Transfer of HEMATOPOIETIC STEM CELLS from BONE MARROW or BLOOD between individuals within the same species (TRANSPLANTATION, HOMOLOGOUS) or transfer within the same individual (TRANSPLANTATION, AUTOLOGOUS). Hematopoietic stem cell transplantation has been used as an alternative to BONE MARROW TRANSPLANTATION in the treatment of a variety of neoplasms.
Transplantation between individuals of the same species. Usually refers to genetically disparate individuals in contradistinction to isogeneic transplantation for genetically identical individuals.
Preparative treatment of transplant recipient with various conditioning regimens including radiation, immune sera, chemotherapy, and/or immunosuppressive agents, prior to transplantation. Transplantation conditioning is very common before bone marrow transplantation.
The clinical entity characterized by anorexia, diarrhea, loss of hair, leukopenia, thrombocytopenia, growth retardation, and eventual death brought about by the GRAFT VS HOST REACTION.
Neoplasms located in the blood and blood-forming tissue (the bone marrow and lymphatic tissue). The commonest forms are the various types of LEUKEMIA, of LYMPHOMA, and of the progressive, life-threatening forms of the MYELODYSPLASTIC SYNDROMES.
Progenitor cells from which all blood cells derive.
Agents that destroy bone marrow activity. They are used to prepare patients for BONE MARROW TRANSPLANTATION or STEM CELL TRANSPLANTATION.
The transfer of STEM CELLS from one individual to another within the same species (TRANSPLANTATION, HOMOLOGOUS) or between species (XENOTRANSPLANTATION), or transfer within the same individual (TRANSPLANTATION, AUTOLOGOUS). The source and location of the stem cells determines their potency or pluripotency to differentiate into various cell types.
Transplantation of an individual's own tissue from one site to another site.
Transplantation of stem cells collected from the peripheral blood. It is a less invasive alternative to direct marrow harvesting of hematopoietic stem cells. Enrichment of stem cells in peripheral blood can be achieved by inducing mobilization of stem cells from the BONE MARROW.
Irradiation of the whole body with ionizing or non-ionizing radiation. It is applicable to humans or animals but not to microorganisms.
Individuals supplying living tissue, organs, cells, blood or blood components for transfer or transplantation to histocompatible recipients.
Providers of tissues for transplant to non-related individuals.
An organism that, as a result of transplantation of donor tissue or cells, consists of two or more cell lines descended from at least two zygotes. This state may result in the induction of donor-specific TRANSPLANTATION TOLERANCE.
The transference of BONE MARROW from one human or animal to another for a variety of purposes including HEMATOPOIETIC STEM CELL TRANSPLANTATION or MESENCHYMAL STEM CELL TRANSPLANTATION.
Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series.
Immunological rejection of tumor tissue/cells following bone marrow transplantation.
Identification of the major histocompatibility antigens of transplant DONORS and potential recipients, usually by serological tests. Donor and recipient pairs should be of identical ABO blood group, and in addition should be matched as closely as possible for HISTOCOMPATIBILITY ANTIGENS in order to minimize the likelihood of allograft rejection. (King, Dictionary of Genetics, 4th ed)
Immunological rejection of leukemia cells following bone marrow transplantation.
Transplantation of STEM CELLS collected from the fetal blood remaining in the UMBILICAL CORD and the PLACENTA after delivery. Included are the HEMATOPOIETIC STEM CELLS.
A nucleoside antibiotic isolated from Streptomyces antibioticus. It has some antineoplastic properties and has broad spectrum activity against DNA viruses in cell cultures and significant antiviral activity against infections caused by a variety of viruses such as the herpes viruses, the VACCINIA VIRUS and varicella zoster virus.
Studies used to test etiologic hypotheses in which inferences about an exposure to putative causal factors are derived from data relating to characteristics of persons under study or to events or experiences in their past. The essential feature is that some of the persons under study have the disease or outcome of interest and their characteristics are compared with those of unaffected persons.
The degree of antigenic similarity between the tissues of different individuals, which determines the acceptance or rejection of allografts.
The occurrence in an individual of two or more cell populations of different chromosomal constitutions, derived from different individuals. This contrasts with MOSAICISM in which the different cell populations are derived from a single individual.
An alkylating agent having a selective immunosuppressive effect on BONE MARROW. It has been used in the palliative treatment of chronic myeloid leukemia (MYELOID LEUKEMIA, CHRONIC), but although symptomatic relief is provided, no permanent remission is brought about. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), busulfan is listed as a known carcinogen.
The return of a sign, symptom, or disease after a remission.
The survival of a graft in a host, the factors responsible for the survival and the changes occurring within the graft during growth in the host.
A progressive, malignant disease of the blood-forming organs, characterized by distorted proliferation and development of leukocytes and their precursors in the blood and bone marrow. Leukemias were originally termed acute or chronic based on life expectancy but now are classified according to cellular maturity. Acute leukemias consist of predominately immature cells; chronic leukemias are composed of more mature cells. (From The Merck Manual, 2006)
Clonal expansion of myeloid blasts in bone marrow, blood, and other tissue. Myeloid leukemias develop from changes in cells that normally produce NEUTROPHILS; BASOPHILS; EOSINOPHILS; and MONOCYTES.
Persons or animals having at least one parent in common. (American College Dictionary, 3d ed)
A class of statistical procedures for estimating the survival function (function of time, starting with a population 100% well at a given time and providing the percentage of the population still well at later times). The survival analysis is then used for making inferences about the effects of treatments, prognostic factors, exposures, and other covariates on the function.
Antigens determined by leukocyte loci found on chromosome 6, the major histocompatibility loci in humans. They are polypeptides or glycoproteins found on most nucleated cells and platelets, determine tissue types for transplantation, and are associated with certain diseases.
Relatively undifferentiated cells that retain the ability to divide and proliferate throughout postnatal life to provide progenitor cells that can differentiate into specialized cells.
Therapeutic act or process that initiates a response to a complete or partial remission level.
Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging.
Clonal hematopoietic stem cell disorders characterized by dysplasia in one or more hematopoietic cell lineages. They predominantly affect patients over 60, are considered preleukemic conditions, and have high probability of transformation into ACUTE MYELOID LEUKEMIA.
The procedure established to evaluate the health status and risk factors of the potential DONORS of biological materials. Donors are selected based on the principles that their health will not be compromised in the process, and the donated materials, such as TISSUES or organs, are safe for reuse in the recipients.
The proportion of survivors in a group, e.g., of patients, studied and followed over a period, or the proportion of persons in a specified group alive at the beginning of a time interval who survive to the end of the interval. It is often studied using life table methods.
Disorders of the blood and blood forming tissues.
Period after successful treatment in which there is no appearance of the symptoms or effects of the disease.
The transference of a part of or an entire liver from one human or animal to another.
Allelic alloantigens often responsible for weak graft rejection in cases when (major) histocompatibility has been established by standard tests. In the mouse they are coded by more than 500 genes at up to 30 minor histocompatibility loci. The most well-known minor histocompatibility antigen in mammals is the H-Y antigen.
The treatment of a disease or condition by several different means simultaneously or sequentially. Chemoimmunotherapy, RADIOIMMUNOTHERAPY, chemoradiotherapy, cryochemotherapy, and SALVAGE THERAPY are seen most frequently, but their combinations with each other and surgery are also used.
Tissues, cells, or organs transplanted between genetically different individuals of the same species.
Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.
Elements of limited time intervals, contributing to particular results or situations.
A neoplasm characterized by abnormalities of the lymphoid cell precursors leading to excessive lymphoblasts in the marrow and other organs. It is the most common cancer in children and accounts for the vast majority of all childhood leukemias.
The development and formation of various types of BLOOD CELLS. Hematopoiesis can take place in the BONE MARROW (medullary) or outside the bone marrow (HEMATOPOIESIS, EXTRAMEDULLARY).
Disease having a short and relatively severe course.
An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient.
Studies in which individuals or populations are followed to assess the outcome of exposures, procedures, or effects of a characteristic, e.g., occurrence of disease.
The release of stem cells from the bone marrow into the peripheral blood circulation for the purpose of leukapheresis, prior to stem cell transplantation. Hematopoietic growth factors or chemotherapeutic agents often are used to stimulate the mobilization.
Clonal hematopoetic disorder caused by an acquired genetic defect in PLURIPOTENT STEM CELLS. It starts in MYELOID CELLS of the bone marrow, invades the blood and then other organs. The condition progresses from a stable, more indolent, chronic phase (LEUKEMIA, MYELOID, CHRONIC PHASE) lasting up to 7 years, to an advanced phase composed of an accelerated phase (LEUKEMIA, MYELOID, ACCELERATED PHASE) and BLAST CRISIS.
Glycoproteins found on immature hematopoietic cells and endothelial cells. They are the only molecules to date whose expression within the blood system is restricted to a small number of progenitor cells in the bone marrow.
Transference of cells within an individual, between individuals of the same species, or between individuals of different species.
A cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation. (From Martindale, The Extra Pharmacopoeia, 30th ed).
Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the LIVER to form the active aldophosphamide. It has been used in the treatment of LYMPHOMA and LEUKEMIA. Its side effect, ALOPECIA, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer.
The transference of a kidney from one human or animal to another.
Deliberate prevention or diminution of the host's immune response. It may be nonspecific as in the administration of immunosuppressive agents (drugs or radiation) or by lymphocyte depletion or may be specific as in desensitization or the simultaneous administration of antigen and immunosuppressive drugs.
A therapeutic approach, involving chemotherapy, radiation therapy, or surgery, after initial regimens have failed to lead to improvement in a patient's condition. Salvage therapy is most often used for neoplastic diseases.
A general term for the complex phenomena involved in allo- and xenograft rejection by a host and graft vs host reaction. Although the reactions involved in transplantation immunology are primarily thymus-dependent phenomena of cellular immunity, humoral factors also play a part in late rejection.
Any of a group of malignant tumors of lymphoid tissue that differ from HODGKIN DISEASE, being more heterogeneous with respect to malignant cell lineage, clinical course, prognosis, and therapy. The only common feature among these tumors is the absence of giant REED-STERNBERG CELLS, a characteristic of Hodgkin's disease.
A malignancy of mature PLASMA CELLS engaging in monoclonal immunoglobulin production. It is characterized by hyperglobulinemia, excess Bence-Jones proteins (free monoclonal IMMUNOGLOBULIN LIGHT CHAINS) in the urine, skeletal destruction, bone pain, and fractures. Other features include ANEMIA; HYPERCALCEMIA; and RENAL INSUFFICIENCY.
Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells.
Immunosuppression by reduction of circulating lymphocytes or by T-cell depletion of bone marrow. The former may be accomplished in vivo by thoracic duct drainage or administration of antilymphocyte serum. The latter is performed ex vivo on bone marrow before its transplantation.
An aspect of personal behavior or lifestyle, environmental exposure, or inborn or inherited characteristic, which, on the basis of epidemiologic evidence, is known to be associated with a health-related condition considered important to prevent.
Disorders characterized by proliferation of lymphoid tissue, general or unspecified.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.
Liver disease that is caused by injuries to the ENDOTHELIAL CELLS of the vessels and subendothelial EDEMA, but not by THROMBOSIS. Extracellular matrix, rich in FIBRONECTINS, is usually deposited around the HEPATIC VEINS leading to venous outflow occlusion and sinusoidal obstruction.
Non-cadaveric providers of organs for transplant to related or non-related recipients.
Transfer of MESENCHYMAL STEM CELLS between individuals within the same species (TRANSPLANTATION, HOMOLOGOUS) or transfer within the same individual (TRANSPLANTATION, AUTOLOGOUS).
A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations.
Infection with CYTOMEGALOVIRUS, characterized by enlarged cells bearing intranuclear inclusions. Infection may be in almost any organ, but the salivary glands are the most common site in children, as are the lungs in adults.
A general term for various neoplastic diseases of the lymphoid tissue.
The transfer of lymphocytes from a donor to a recipient or reinfusion to the donor.
Transplantation between genetically identical individuals, i.e., members of the same species with identical histocompatibility antigens, such as monozygotic twins, members of the same inbred strain, or members of a hybrid population produced by crossing certain inbred strains.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro.
The use of two or more chemicals simultaneously or sequentially in the drug therapy of neoplasms. The drugs need not be in the same dosage form.
Serum containing GAMMA-GLOBULINS which are antibodies for lymphocyte ANTIGENS. It is used both as a test for HISTOCOMPATIBILITY and therapeutically in TRANSPLANTATION.
An antibiotic substance derived from Penicillium stoloniferum, and related species. It blocks de novo biosynthesis of purine nucleotides by inhibition of the enzyme inosine monophosphate dehydrogenase. Mycophenolic acid is important because of its selective effects on the immune system. It prevents the proliferation of T-cells, lymphocytes, and the formation of antibodies from B-cells. It also may inhibit recruitment of leukocytes to inflammatory sites. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p1301)
Diseases which have one or more of the following characteristics: they are permanent, leave residual disability, are caused by nonreversible pathological alteration, require special training of the patient for rehabilitation, or may be expected to require a long period of supervision, observation, or care. (Dictionary of Health Services Management, 2d ed)
Transference of a tissue or organ from either an alive or deceased donor, within an individual, between individuals of the same species, or between individuals of different species.
A form of anemia in which the bone marrow fails to produce adequate numbers of peripheral blood elements.
Group of rare congenital disorders characterized by impairment of both humoral and cell-mediated immunity, leukopenia, and low or absent antibody levels. It is inherited as an X-linked or autosomal recessive defect. Mutations occurring in many different genes cause human Severe Combined Immunodeficiency (SCID).
The ability of tumors to evade destruction by the IMMUNE SYSTEM. Theories concerning possible mechanisms by which this takes place involve both cellular immunity (IMMUNITY, CELLULAR) and humoral immunity (ANTIBODY FORMATION), and also costimulatory pathways related to CD28 antigens (ANTIGENS, CD28) and CD80 antigens (ANTIGENS, CD80).
The transference of a heart from one human or animal to another.
The developmental history of specific differentiated cell types as traced back to the original STEM CELLS in the embryo.
An alkylating nitrogen mustard that is used as an antineoplastic in the form of the levo isomer - MELPHALAN, the racemic mixture - MERPHALAN, and the dextro isomer - MEDPHALAN; toxic to bone marrow, but little vesicant action; potential carcinogen.
Blood of the fetus. Exchange of nutrients and waste between the fetal and maternal blood occurs via the PLACENTA. The cord blood is blood contained in the umbilical vessels (UMBILICAL CORD) at the time of delivery.
The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells.
A critical subpopulation of regulatory T-lymphocytes involved in MHC Class I-restricted interactions. They include both cytotoxic T-lymphocytes (T-LYMPHOCYTES, CYTOTOXIC) and CD8+ suppressor T-lymphocytes.
A neoplasm composed entirely of GRANULOSA CELLS, occurring mostly in the OVARY. In the adult form, it may contain some THECA CELLS. This tumor often produces ESTRADIOL and INHIBIN. The excess estrogen exposure can lead to other malignancies in women and PRECOCIOUS PUBERTY in girls. In rare cases, granulosa cell tumors have been identified in the TESTES.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
The transference of either one or both of the lungs from one human or animal to another.
A bone tumor composed of cellular spindle-cell stroma containing scattered multinucleated giant cells resembling osteoclasts. The tumors range from benign to frankly malignant lesions. The tumor occurs most frequently in an end of a long tubular bone in young adults. (From Dorland, 27th ed; Stedman, 25th ed)
Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics.
Age as a constituent element or influence contributing to the production of a result. It may be applicable to the cause or the effect of a circumstance. It is used with human or animal concepts but should be differentiated from AGING, a physiological process, and TIME FACTORS which refers only to the passage of time.
Transference of an organ between individuals of the same species or between individuals of different species.
New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
Persons who have experienced a prolonged survival after serious disease or who continue to live with a usually life-threatening condition as well as family members, significant others, or individuals surviving traumatic life events.
Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group.
The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from PREVALENCE, which refers to all cases, new or old, in the population at a given time.
A glycoprotein of MW 25 kDa containing internal disulfide bonds. It induces the survival, proliferation, and differentiation of neutrophilic granulocyte precursor cells and functionally activates mature blood neutrophils. Among the family of colony-stimulating factors, G-CSF is the most potent inducer of terminal differentiation to granulocytes and macrophages of leukemic myeloid cell lines.
Cells derived from the BLASTOCYST INNER CELL MASS which forms before implantation in the uterine wall. They retain the ability to divide, proliferate and provide progenitor cells that can differentiate into specialized cells.
A cytologic technique for measuring the functional capacity of stem cells by assaying their activity.
A particular zone of tissue composed of a specialized microenvironment where stem cells are retained in a undifferentiated, self-renewable state.
Cells with high proliferative and self renewal capacities derived from adults.
Bone marrow-derived lymphocytes that possess cytotoxic properties, classically directed against transformed and virus-infected cells. Unlike T CELLS; and B CELLS; NK CELLS are not antigen specific. The cytotoxicity of natural killer cells is determined by the collective signaling of an array of inhibitory and stimulatory CELL SURFACE RECEPTORS. A subset of T-LYMPHOCYTES referred to as NATURAL KILLER T CELLS shares some of the properties of this cell type.
Form of leukemia characterized by an uncontrolled proliferation of the myeloid lineage and their precursors (MYELOID PROGENITOR CELLS) in the bone marrow and other sites.
Invasion of the host organism by microorganisms that can cause pathological conditions or diseases.
Tumors of bone tissue or synovial or other soft tissue characterized by the presence of giant cells. The most common are giant cell tumor of tendon sheath and GIANT CELL TUMOR OF BONE.
Remnant of a tumor or cancer after primary, potentially curative therapy. (Dr. Daniel Masys, written communication)
Mice homozygous for the mutant autosomal recessive gene "scid" which is located on the centromeric end of chromosome 16. These mice lack mature, functional lymphocytes and are thus highly susceptible to lethal opportunistic infections if not chronically treated with antibiotics. The lack of B- and T-cell immunity resembles severe combined immunodeficiency (SCID) syndrome in human infants. SCID mice are useful as animal models since they are receptive to implantation of a human immune system producing SCID-human (SCID-hu) hematochimeric mice.
The blood-making organs and tissues, principally the bone marrow and lymph nodes.
Neoplasms composed of primordial GERM CELLS of embryonic GONADS or of elements of the germ layers of the EMBRYO, MAMMALIAN. The concept does not refer to neoplasms located in the gonads or present in an embryo or FETUS.
The transference of pancreatic islets within an individual, between individuals of the same species, or between individuals of different species.
The mechanism by which latent viruses, such as genetically transmitted tumor viruses (PROVIRUSES) or PROPHAGES of lysogenic bacteria, are induced to replicate and then released as infectious viruses. It may be effected by various endogenous and exogenous stimuli, including B-cell LIPOPOLYSACCHARIDES, glucocorticoid hormones, halogenated pyrimidines, IONIZING RADIATION, ultraviolet light, and superinfecting viruses.
A malignant disease characterized by progressive enlargement of the lymph nodes, spleen, and general lymphoid tissue. In the classical variant, giant usually multinucleate Hodgkin's and REED-STERNBERG CELLS are present; in the nodular lymphocyte predominant variant, lymphocytic and histiocytic cells are seen.
Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.
Transplantation between animals of different species.
A genus of the family HERPESVIRIDAE, subfamily BETAHERPESVIRINAE, infecting the salivary glands, liver, spleen, lungs, eyes, and other organs, in which they produce characteristically enlarged cells with intranuclear inclusions. Infection with Cytomegalovirus is also seen as an opportunistic infection in AIDS.
An induced state of non-reactivity to grafted tissue from a donor organism that would ordinarily trigger a cell-mediated or humoral immune response.
Bone-marrow-derived, non-hematopoietic cells that support HEMATOPOETIC STEM CELLS. They have also been isolated from other organs and tissues such as UMBILICAL CORD BLOOD, umbilical vein subendothelium, and WHARTON JELLY. These cells are considered to be a source of multipotent stem cells because they include subpopulations of mesenchymal stem cells.
Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection.
The body's defense mechanism against foreign organisms or substances and deviant native cells. It includes the humoral immune response and the cell-mediated response and consists of a complex of interrelated cellular, molecular, and genetic components.
A human or animal whose immunologic mechanism is deficient because of an immunodeficiency disorder or other disease or as the result of the administration of immunosuppressive drugs or radiation.
Antibodies produced by a single clone of cells.
Infection with ROSEOLOVIRUS, the most common in humans being EXANTHEMA SUBITUM, a benign disease of infants and young children.
Systemic lysosomal storage disease caused by a deficiency of alpha-L-iduronidase (IDURONIDASE) and characterized by progressive physical deterioration with urinary excretion of DERMATAN SULFATE and HEPARAN SULFATE. There are three recognized phenotypes representing a spectrum of clinical severity from severe to mild: Hurler syndrome, Hurler-Scheie syndrome and Scheie syndrome (formerly mucopolysaccharidosis V). Symptoms may include DWARFISM; hepatosplenomegaly; thick, coarse facial features with low nasal bridge; corneal clouding; cardiac complications; and noisy breathing.
Tumors or cancer of the TESTIS. Germ cell tumors (GERMINOMA) of the testis constitute 95% of all testicular neoplasms.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression.
Unusual tumor affecting any site of the body, but most often encountered in the head and neck. Considerable debate has surrounded the histogenesis of this neoplasm; however, it is considered to be a myoblastoma of, usually, a benign nature. It affects women more often than men. When it develops beneath the epidermis or mucous membrane, it can lead to proliferation of the squamous cells and mimic squamous cell carcinoma.
Death resulting from the presence of a disease in an individual, as shown by a single case report or a limited number of patients. This should be differentiated from DEATH, the physiological cessation of life and from MORTALITY, an epidemiological or statistical concept.
Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.
A hematopoietic growth factor and the ligand of the cell surface c-kit protein (PROTO-ONCOGENE PROTEINS C-KIT). It is expressed during embryogenesis and is a growth factor for a number of cell types including the MAST CELLS and the MELANOCYTES in addition to the HEMATOPOIETIC STEM CELLS.
A cell line derived from cultured tumor cells.
A pyrimidine nucleoside analog that is used mainly in the treatment of leukemia, especially acute non-lymphoblastic leukemia. Cytarabine is an antimetabolite antineoplastic agent that inhibits the synthesis of DNA. Its actions are specific for the S phase of the cell cycle. It also has antiviral and immunosuppressant properties. (From Martindale, The Extra Pharmacopoeia, 30th ed, p472)
The specific failure of a normally responsive individual to make an immune response to a known antigen. It results from previous contact with the antigen by an immunologically immature individual (fetus or neonate) or by an adult exposed to extreme high-dose or low-dose antigen, or by exposure to radiation, antimetabolites, antilymphocytic serum, etc.
A set of techniques used when variation in several variables has to be studied simultaneously. In statistics, multivariate analysis is interpreted as any analytic method that allows simultaneous study of two or more dependent variables.
Tissue, organ, or gamete donation intended for a designated recipient.
A family of receptors found on NK CELLS that have specificity for a variety of HLA ANTIGENS. KIR receptors contain up to three different extracellular immunoglobulin-like domains referred to as D0, D1, and D2 and play an important role in blocking NK cell activation against cells expressing the appropriate HLA antigens thus preventing cell lysis. Although they are often referred to as being inhibitory receptors, a subset of KIR receptors may also play an activating role in NK cells.
A semisynthetic derivative of PODOPHYLLOTOXIN that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle.
CD4-positive T cells that inhibit immunopathology or autoimmune disease in vivo. They inhibit the immune response by influencing the activity of other cell types. Regulatory T-cells include naturally occurring CD4+CD25+ cells, IL-10 secreting Tr1 cells, and Th3 cells.
The cells found in the body fluid circulating throughout the CARDIOVASCULAR SYSTEM.
Process of classifying cells of the immune system based on structural and functional differences. The process is commonly used to analyze and sort T-lymphocytes into subsets based on CD antigens by the technique of flow cytometry.
A critical subpopulation of T-lymphocytes involved in the induction of most immunological functions. The HIV virus has selective tropism for the T4 cell which expresses the CD4 phenotypic marker, a receptor for HIV. In fact, the key element in the profound immunosuppression seen in HIV infection is the depletion of this subset of T-lymphocytes.
In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.
The transference of a pancreas from one human or animal to another.
Specialized stem cells that are committed to give rise to cells that have a particular function; examples are MYOBLASTS; MYELOID PROGENITOR CELLS; and skin stem cells. (Stem Cells: A Primer [Internet]. Bethesda (MD): National Institutes of Health (US); 2000 May [cited 2002 Apr 5]. Available from:
A strain of non-obese diabetic mice developed in Japan that has been widely studied as a model for T-cell-dependent autoimmune insulin-dependent diabetes mellitus in which insulitis is a major histopathologic feature, and in which genetic susceptibility is strongly MHC-linked.
Methods for maintaining or growing CELLS in vitro.
Gonadal neoplasm composed entirely of SERTOLI CELLS or may have a component of GRANULOSA CELLS. Some of the Sertoli cell tumors produce ESTROGEN or ANDROGENS, but seldom in sufficient quantity to cause clinical symptoms such as FEMINIZATION or masculinization (VIRILISM).
Congenital disorder affecting all bone marrow elements, resulting in ANEMIA; LEUKOPENIA; and THROMBOPENIA, and associated with cardiac, renal, and limb malformations as well as dermal pigmentary changes. Spontaneous CHROMOSOME BREAKAGE is a feature of this disease along with predisposition to LEUKEMIA. There are at least 7 complementation groups in Fanconi anemia: FANCA, FANCB, FANCC, FANCD1, FANCD2, FANCE, FANCF, FANCG, and FANCL. (from Online Mendelian Inheritance in Man,, August 20, 2004)
Cells that can give rise to cells of the three different GERM LAYERS.
Cells derived from a FETUS that retain the ability to divide, proliferate and provide progenitor cells that can differentiate into specialized cells.
The theory that T-cells monitor cell surfaces and detect structural changes in the plasma membrane and/or surface antigens of virally or neoplastically transformed cells.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
An encapsulated lymphatic organ through which venous blood filters.
An antigenic mismatch between donor and recipient blood. Antibodies present in the recipient's serum may be directed against antigens in the donor product. Such a mismatch may result in a transfusion reaction in which, for example, donor blood is hemolyzed. (From Saunders Dictionary & Encyclopedia of Laboratory Medicine and Technology, 1984).
An organism whose body contains cell populations of different genotypes as a result of the TRANSPLANTATION of donor cells after sufficient ionizing radiation to destroy the mature recipient's cells which would otherwise reject the donor cells.
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
A class of drugs that differs from other alkylating agents used clinically in that they are monofunctional and thus unable to cross-link cellular macromolecules. Among their common properties are a requirement for metabolic activation to intermediates with antitumor efficacy and the presence in their chemical structures of N-methyl groups, that after metabolism, can covalently modify cellular DNA. The precise mechanisms by which each of these drugs acts to kill tumor cells are not completely understood. (From AMA, Drug Evaluations Annual, 1994, p2026)
Form of adoptive transfer where cells with antitumor activity are transferred to the tumor-bearing host in order to mediate tumor regression. The lymphoid cells commonly used are lymphokine-activated killer (LAK) cells and tumor-infiltrating lymphocytes (TIL). This is usually considered a form of passive immunotherapy. (From DeVita, et al., Cancer, 1993, pp.305-7, 314)
Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.
Pathologic processes that affect patients after a surgical procedure. They may or may not be related to the disease for which the surgery was done, and they may or may not be direct results of the surgery.
The classes of BONE MARROW-derived blood cells in the monocytic series (MONOCYTES and their precursors) and granulocytic series (GRANULOCYTES and their precursors).
Formation of LYMPHOCYTES and PLASMA CELLS from the lymphoid stem cells which develop from the pluripotent HEMATOPOIETIC STEM CELLS in the BONE MARROW. These lymphoid stem cells differentiate into T-LYMPHOCYTES; B-LYMPHOCYTES; PLASMA CELLS; or NK-cells (KILLER CELLS, NATURAL) depending on the organ or tissues (LYMPHOID TISSUE) to which they migrate.
Transference of fetal tissue between individuals of the same species or between individuals of different species.
A nonparametric method of compiling LIFE TABLES or survival tables. It combines calculated probabilities of survival and estimates to allow for observations occurring beyond a measurement threshold, which are assumed to occur randomly. Time intervals are defined as ending each time an event occurs and are therefore unequal. (From Last, A Dictionary of Epidemiology, 1995)
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
The local recurrence of a neoplasm following treatment. It arises from microscopic cells of the original neoplasm that have escaped therapeutic intervention and later become clinically visible at the original site.
A single, unpaired primary lymphoid organ situated in the MEDIASTINUM, extending superiorly into the neck to the lower edge of the THYROID GLAND and inferiorly to the fourth costal cartilage. It is necessary for normal development of immunologic function early in life. By puberty, it begins to involute and much of the tissue is replaced by fat.
INFLAMMATION of the soft tissues of the MOUTH, such as MUCOSA; PALATE; GINGIVA; and LIP.
The preparation of leukocyte concentrates with the return of red cells and leukocyte-poor plasma to the donor.
Abnormal growths of tissue that follow a previous neoplasm but are not metastases of the latter. The second neoplasm may have the same or different histological type and can occur in the same or different organs as the previous neoplasm but in all cases arises from an independent oncogenic event. The development of the second neoplasm may or may not be related to the treatment for the previous neoplasm since genetic risk or predisposing factors may actually be the cause.
A very toxic alkylating antineoplastic agent also used as an insect sterilant. It causes skin, gastrointestinal, CNS, and bone marrow damage. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), thiotepa may reasonably be anticipated to be a carcinogen (Merck Index, 11th ed).
Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.
Techniques and strategies which include the use of coding sequences and other conventional or radical means to transform or modify cells for the purpose of treating or reversing disease conditions.
Self-renewing cells that generate the main phenotypes of the nervous system in both the embryo and adult. Neural stem cells are precursors to both NEURONS and NEUROGLIA.
The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
High-molecular weight glycoproteins uniquely expressed on the surface of LEUKOCYTES and their hemopoietic progenitors. They contain a cytoplasmic protein tyrosine phosphatase activity which plays a role in intracellular signaling from the CELL SURFACE RECEPTORS. The CD45 antigens occur as multiple isoforms that result from alternative mRNA splicing and differential usage of three exons.
The number of CELLS of a specific kind, usually measured per unit volume or area of sample.
A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.
The physiological renewal, repair, or replacement of tissue.
White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS.
Gonadal interstitial or stromal cell neoplasm composed of only LEYDIG CELLS. These tumors may produce one or more of the steroid hormones such as ANDROGENS; ESTROGENS; and CORTICOSTEROIDS. Clinical symptoms include testicular swelling, GYNECOMASTIA, sexual precocity in children, or virilization (VIRILISM) in females.
Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as SKIN and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process ANTIGENS, and present them to T-CELLS, thereby stimulating CELL-MEDIATED IMMUNITY. They are different from the non-hematopoietic FOLLICULAR DENDRITIC CELLS, which have a similar morphology and immune system function, but with respect to humoral immunity (ANTIBODY PRODUCTION).
Established cell cultures that have the potential to propagate indefinitely.
DNA molecules capable of autonomous replication within a host cell and into which other DNA sequences can be inserted and thus amplified. Many are derived from PLASMIDS; BACTERIOPHAGES; or VIRUSES. They are used for transporting foreign genes into recipient cells. Genetic vectors possess a functional replicator site and contain GENETIC MARKERS to facilitate their selective recognition.
A protein-tyrosine kinase receptor that is specific for STEM CELL FACTOR. This interaction is crucial for the development of hematopoietic, gonadal, and pigment stem cells. Genetic mutations that disrupt the expression of PROTO-ONCOGENE PROTEINS C-KIT are associated with PIEBALDISM, while overexpression or constitutive activation of the c-kit protein-tyrosine kinase is associated with tumorigenesis.
T cells associate with and predict leukemia relapse in AML patients post allogeneic stem cell transplantation". Blood Cancer ... Cytotoxic T cells (TC cells, CTLs, T-killer cells, killer T cells) destroy virus-infected cells and tumor cells, and are also ... Haematopoietic progenitors (lymphoid progenitor cells) from haematopoietic stem cells populate the thymus and expand by cell ... Natural killer T cells (NKT cells - not to be confused with natural killer cells of the innate immune system) bridge the ...
... which allows for the destruction of harmful tumor cells. In mice, allogeneic stem cell transplantation donor CD8+ T cells ... The consequences of an immune response are seen in allogeneic hematopoietic stem cell transplantation (HCT) when the peptides ... The lack of recognition of a T cell to this self antigen is the reason why allogeneic stem cell transplantation for an HLA ... but is exposed to the HA-1 peptide during pregnancy or allogeneic stem cell transplantation. During pregnancy, the fetal HA-1 ...
... and an immune response against, tumor cells. All T cells originate from c-kit+Sca1+ haematopoietic stem cells (HSC) which ... T cells associate with and predict leukemia relapse in AML patients post allogeneic stem cell transplantation". Blood Cancer ... Cytotoxic T cells (TC cells, CTLs, T-killer cells, killer T cells) destroy virus-infected cells and tumor cells, and are also ... on their cell surface. T cells are born from hematopoietic stem cells, found in the bone marrow. Then, developing T cells ...
... which will be reinitiated by donor's stem cells soon after transplantation, and will play a role as recipient-versus-tumor (RVT ... as well as the challenge to find HLA-matched donors for conventional hematopoietic stem cell transplantation, Dr Huisheng Ai, ... The cells employed are allogeneic peripheral blood stem cells. Matched HLA between donor and recipient is not necessary. The ... less-toxic cells processed prior to transplantation, and the preservation of host immune system that is capable of resisting ...
T cells associate with and predict leukemia relapse in AML patients post allogeneic stem cell transplantation". Blood Cancer ... and an immune response against, tumour cells. ... All T cells originate from c-kit+Sca1+ haematopoietic stem ... Cytotoxic T cells (TC cells, CTLs, T-killer cells, killer T cells) destroy virus-infected cells and tumor cells, and are also ... Helper CD4+ T cellsEdit. T helper cells (TH cells) assist other lymphocytes, including maturation of B cells into plasma cells ...
Allogeneic hematopoietic stem cell transplantation ("bone marrow transplantation" from a genetically non-identical donor) can ... since the donor's immune cells will often attack the tumor in a phenomenon known as graft-versus-tumor effect. For this reason ... Most cells in the body grow and divide to form new cells. But cancer cells grow and divide faster than many of the normal cells ... of immune cells; interrupting T-cell signaling required to mount an immune response; inhibiting the production of anti-cancer ...
... to augment an anti-tumor immune response or ensure that the donor stem cells remain engrafted. These donated white blood cells ... Loren AW, Porter DL (2006). "Donor leukocyte infusions after unrelated donor hematopoietic stem cell transplantation". Current ... "Donor lymphocyte infusions to treat hematologic malignancies in relapse after allogeneic blood or marrow transplantation". ... or buffy coat infusion is a form of adoptive immunotherapy used after hematopoietic stem cell transplantation. Formerly, the ...
In general, by transfusing healthy stem cells to the recipient's bloodstream to reform a healthy immune system, allogeneic ... 2005). "Graft-versus-tumor effects after allogeneic hematopoietic cell transplantation with nonmyeloablative conditioning". J. ... Hematopoietic stem cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived ... "Peripheral blood stem cells for allogeneic transplantation: a review". Stem Cells. 19 (2): 108-17. doi:10.1634/stemcells.19-2- ...
"Anti-Viral Central Memory CD8 Veto Cells in Haploidentical Hematopoietic Stem Cell Transplantation - ICH GCP - Clinical Trials ... In the immune system, veto cells are white blood cells that have a selective immunomodulation properties. Veto cells were first ... Veto cell administration can also be used for tolerance induction to allogeneic/haploidentical solid organ grafts. This has ... Anti-3rd party veto cells have also been shown to have Graft-versus-tumor effect Ophir, Eran; Reisner, Yair (2012-05-02). "The ...
... appears after allogeneic hematopoietic stem cell transplantation (HSCT). The graft contains donor T cells (T lymphocytes) that ... GvT might develop after recognizing tumor-specific or recipient-specific alloantigens. It could lead to remission or immune ... March 2005). "Graft-versus-tumor effects after allogeneic hematopoietic cell transplantation with nonmyeloablative conditioning ... Graft-versus-host disease Hematopoietic stem cell transplantation Thompson LF, Tsukamoto H, Chernogorova P, Zeiser R (January ...
T cells associate with and predict leukemia relapse in AML patients post allogeneic stem cell transplantation. Blood Cancer ... activity associates with acute B lymphoblastic leukemia relapse after allogeneic hematopoietic stem cell transplantation. ... T Cells to protect tumour cells. Nature Communications. March 2018, 9 (1): 948. PMC 5838096. PMID 29507342. doi:10.1038/s41467- ... Immune inhibitory molecules LAG-3 and PD-1 synergistically regulate T-cell function to promote tumoral immune escape. Cancer ...
... requiring rescue by transplantation of a new immune system (hematopoietic stem cell transplantation), using either autologous ... The tumor cells accumulate in the lymphoid system, including lymph nodes and the spleen, with non-useful cells eventually ... stem cell transplantation, or those from a matched donor (an allogeneic stem cell transplant). A presentation at the December ... Of the evaluable population, approximately 18% were treated with high-dose therapy and stem cell transplantation in first ...
"Adoptive transfer of T-cell precursors enhances T-cell reconstitution after allogeneic hematopoietic stem cell transplantation ... "IL-22 protects intestinal stem cells from immune-mediated tissue damage and regulates sensitivity to graft vs. host disease". ... "Tumor immunotherapy across MHC barriers using allogeneic T-cell precursors". Nature Biotechnology 2008; 4:453-461. (commentary ... "Nrf2 regulates haematopoietic stem cell function". Nature Cell Biology. 2013; 15(3): 309-16. PMID 23434824; PMC 3699879. Hanash ...
... power to make haploidentical hematopoietic stem cell transplantation a safe modality for induction of immune tolerance". ... These veto cells can also exert graft vs tumor effect. CD4+ T cell depletion is one of two hallmarks of HIV. Depletion of ... Saad, Ayman; Lamb, Lawrence (2017). "Ex vivo T-cell depletion in allogeneic hematopoietic stem cell transplant: past, present ... In haploidentical hematopoietic stem cell transplantation, in vivo TCD suppressed lymphocytes early on. However, the incidence ...
"Outcomes of allogeneic stem cell transplantation in hepatosplenic T-cell lymphoma". Blood Cancer Journal. 5 (6): e318. doi: ... Pathology and genetics of tumours of haematopoietic and lymphoid tissues. World Health Organization Classification of Tumors. 3 ... except in the case of an allogeneic stem cell transplant. It is a systemic neoplasm comprising medium-sized cytotoxic T-cells ... an association that has led to the hypothesis that long-term immune stimulation in the setting of immunosuppression is the ...
... and tacrolimus/sirolimus as graft-versus-host disease prophylaxis after allogeneic hematopoietic stem cell transplantation". ... GvHD is commonly associated with bone marrow transplants and stem cell transplants. White blood cells of the donor's immune ... donor T-cells have proven to have a valuable graft-versus-tumor effect. A great deal of current research on allogeneic bone ... Prior to haematopoietic stem cell transplantation, radiation or chemotherapy results in damage and activation of host tissues, ...
Hypogammaglobulinaemia in patients pre‑ and post‑allogeneic hematopoietic stem cell transplantation (HSCT). A form of ... hyaluronidases help cancer cells escape from primary tumor masses. However, studies show that removal of hyaluronan from tumors ... It is an immune globulin with a recombinant human hyaluronidase indicated in the United States for the treatment of primary ... "Mouse sperm lacking cell surface hyaluronidase PH-20 can pass through the layer of cumulus cells and fertilize the egg". The ...
... is a major barrier for allogeneic stem cell transplant because of the immune reactions of donor T cell against the person ... a high dose cyclophosphamide post-transplant in a half matched or haploidentical donor hematopoietic stem cell transplantation ... Suggested mechanisms include: Elimination of T regulatory cells (CD4+CD25+ T cells) in naive and tumor-bearing hosts Induction ... Or-Geva N, Reisner Y (March 2016). "The evolution of T-cell depletion in haploidentical stem-cell transplantation". British ...
2013). Towards effective and safe immunotherapy after allogeneic stem cell transplantation: identification of hematopoietic- ... producing cells, and blood cells. This supports the association of KIAA1551 with the functioning immune system. KIAA1551 is ... doi:10.1016/j.cell.2015.06.043. Bennett, R. D., Pittelkow, M. R., & Strehler, E. E. (2013). Immunolocalization of the tumor- ... NANOG was also found to be an essential transcription factor in embryonic stem cells, specifically involved in gene expression ...
... although several different cell types have been identified, such as various immune lineages, mesenchymal stem cells, and ... "Fetomaternal Microchimerism Is Associated with Better Outcome in Haploidentical Hematopoietic Stem Cell Transplantation". Blood ... Microchimeric cells also cluster several times more in lung tumors than in surrounding healthy lung tissue. Fetal cells from ... Apparently, women with breast cancer may fail in the process of obtaining and maintaining allogeneic fetal cells. Low ...
Virus-specific T-Lymphocytes (VST) therapy is used for patients who have received hematopoietic stem cell transplantation that ... cell responses to mitogens and allogeneic cells, cytokine production by cells Tests for B cell function: antibodies to routine ... Immune deficiencies can result in persistent or recurring infections, autoinflammatory disorders, tumors, and disorders of ... June 2008). "Stem cell transplantation for primary immunodeficiencies". Bone Marrow Transplant. 41 Suppl 2: S83-6. doi:10.1038/ ...
... allogeneic stem cell transplantation 2007 Effects of mesenchymal stem cells on cell cycle and apoptosis of hematopoietic tissue ... tumor antigen 1-specific T lymphocyte generation soon after nonmyeloablative allergenic stem-cell transplantation in acute and ... mesenchymal stem cells homed to thymus inducing immune recovery of mice after haploidentical bone marrow transplantation", ... platform in China Prophylactic G-CSF mobilized donor lymphocytes infusion after non-myeloablative stem celltransplantation ...
... based on either autologous hematopoietic stem cell transplantation or more recently using multi-potent mesenchymal stem cells ( ... for safer allogeneic stem cell transplantation for every patient in need with hematological malignancies and solid tumors as ... Israeli cell therapy tricks immune system into fighting cancer Israel21c Stem cell therapy trial for ALS and MS patients at ... or non-myeloablative stem cell transplantation (NST) were pioneered by Slavin for safer stem cell transplantation for treatment ...
"New perspectives on the use of mTOR inhibitors in allogeneic haematopoietic stem cell transplantation and graft-versus-host ... When dosed appropriately, sirolimus can enhance the immune response to tumor targeting or otherwise promote tumor regression in ... It inhibits activation of T cells and B cells by reducing their sensitivity to interleukin-2 (IL-2) through mTOR inhibition. It ... a complication of hematopoietic stem cell transplantation. While contrasted results were obtained in clinical trials, pre- ...
The number of pregnancies observed after hematopoietic stem cell transplantation involving such a procedure is lower than 2%. ... and allogeneic peripheral blood stem cell transplant". Bone Marrow Transplant. 40 (6): 573-8. doi:10.1038/sj.bmt.1705771. PMID ... Total body irradiation in the setting of bone marrow transplantation serves to destroy or suppress the recipient's immune ... preventing immunologic rejection of transplanted donor bone marrow or blood stem cells. Additionally, high doses of total body ...
Stem cells are also in clinical phases for treatment in ophthalmology. Hematopoietic stem cells have been used to treat corneal ... based on the creation of a disease-resistant immune system through transplantation of autologous, gene-modified (HIV-1- ... There are two main categories of stem cells used for treatments: allogeneic stem cells derived from a genetically different ... There was also no tumor formation seen during the three-month experimental period. Long-term studies need to be carried out to ...
As of 2016[update], the only established therapy using stem cells is hematopoietic stem cell transplantation. This usually ... There are two main categories of stem cells used for treatments: allogeneic stem cells derived from a genetically different ... The transplanted cells also generate an immune response that helps to kill off the cancer cells; this process can go too far, ... There was also no tumor formation seen during the three-month experimental period. Long-term studies need to be carried out to ...
... subtype of ALL is frequently resistant to the combination of chemotherapy and TKIs and allogeneic stem cell transplantation is ... stromal cells as treatment or prophylaxis for acute or chronic graft-versus-host disease in haematopoietic stem cell transplant ... The process as a whole results in an effector cell, typically a T-cell, that can recognize a tumor cell antigen in a manner ... The final transgene sequence, containing the scFv and endodomain sequences is then inserted into immune effector cells that are ...
... and allogeneic stem cell transplant, where the stem cells come from a donor that matches the person's HLA type to prevent the ... "High-Dose Chemotherapy With Autologous Hematopoietic Stem-Cell Transplantation in Metastatic Breast Cancer: Overview of Six ... "CAR T Cells: Engineering Patients' Immune Cells to Treat Their Cancers". National Cancer Institute. National Institutes of ... but clinical trials are still in development as to whether CAR T-cell therapy can be effective against solid tumor cancers, ...
Purchase Immune Biology of Allogeneic Hematopoietic Stem Cell Transplantation - 2nd Edition. Print Book & E-Book. ISBN ... 6. Immune regeneration or immune recovery. 7. Tumor associated antigens. 8. Genetically engineered T cell therapies and immune ... B and T cells in chronic GVHD. 16. NK. 17. Cytokines. 18. Chemokines. 19. Metabolism and intracellular sensor. 20. Omics. 21. ... Immune Biology of Allogeneic Hematopoietic Stem Cell Transplantation 2nd Edition. Models in Discovery and Translation. 0 star ...
Chapter 7 - Tumor-Associated Antigens. Immune Biologic Allogeneic Hematopoeitic Stem cell Transplantation. 2019(2):107-125. ... Novel Tumor Targeting.... *Uses antigens (markers on cells) to specifically target cells that express the marker, including ... The ideal antigen is present on cancer cells but not on normal cells.1 ... Novel Tumor Targeting. AbbVie is leveraging its areas of strength to investigate therapies that are designed to target markers ...
... have a central role in tumor cells surveillance as demonstrated in the setting of allogenic stem cell transplantation. ... Immune system has a key role in tumor surveillance. Nonetheless, tumor cells evade the specific T-lymphocyte mediated immune ... Immune system has a key role in tumor surveillance. Nonetheless, tumor cells evade the specific T-lymphocyte mediated immune ... have a central role in tumor cells surveillance as demonstrated in the setting of allogenic stem cell transplantation. ...
... most hematopoeitic stem cell transplantation procedures have been performed with stem cells collected from the peripheral blood ... and indicates that allogeneic HSCT is a form of immunotherapy. Graft vs tumor is also the major mechanism of benefit of non- ... It is an attack of the "new" bone marrows immune cells against the recipients tissues. This can occur even if the donor and ... Hematopoietic stem cell transplantation (HSCT) or Bone marrow transplantation is a medical procedure in the field of hematology ...
Natural killer (NK) cells are immune cells that recognize and kill virally infected cells and tumor cells. NK cells are ... Allogeneic hematopoietic stem cell transplantation (HSCT) is a very effective treatment for a number of hematological ... CD56+CD3- NK Cells Following Allogeneic Stem Cell Transplantation. The safety and scientific validity of this study is the ... Allogeneic Stem Cell Transplant CD56+CD3- NK Cells Procedure: Infusion of donor derived ex-vivo selected NK cells to patients ...
... of immune function using blood cells and sera obtained from patients after vaccination following hematopoietic stem cell ... Furthermore, this prolonged deficit in T cell function decreases the effectiveness of vaccination against tumour antigens and ... and relapse has been shown to be inversely proportional to T cell reconstitution following both autologous and allogeneic HSCT ... Studies of the Immune Response to Vaccination After Hematopoietic Stem Cell Transplantation. This study has been completed. ...
... demonstrable anti-autoimmunity mediated by allogeneic immune cells favorably affects outcome after stem cell transplantation in ... was the discovery of the immune-mediated allogeneic graft-versus-tumor (GVT) effect (4, 5). The importance of this effect was ... Nonmyeloablative allogeneic hematopoietic stem cell transplantation for autoimmune disease. Authors. *. Steven Z. Pavletic. ... Alois Gratwohl, Allogeneic hematopoietic stem cell transplantation for severe autoimmune diseases, Autoimmunity, 2008, 41, 8, ...
tumor (GVT) effect to eliminate residual malignant cells after allogeneic hematopoietic stem cell transplantation (HSCT). In ... perception of NK cells as innate effector cells with anti-tumor effects in the setting of allogeneic stem cell transplantation ... effect to eliminate residual malignant cells after allogeneic hematopoietic stem cell transplantation (HSCT). In this ... and NK cell subsets in 88 recipients of peripheral blood stem cell grafts with multicolor flowcytometry. Our primary aim was to ...
... curative graft-versus-myeloma activity observed in some patients following allogeneic hematopoietic stem cell transplantation ... T cells and NK1.1+ cells was conducted in tumor-bearing mice before ALT-803 treatment. Effective depletion of these immune cell ... effector cells versus target cells alone or target cells + KO effector cells versus target cells + WT effector cells under the ... Hematopoietic stem cell transplantation for multiple myeloma beyond 2010. Blood 2010;115:3655-63. ...
Find out how a bone marrow transplant restores the bone marrows ability to create normal, hematopoietic stem cells. ... autologous stem cell transplants and allogeneic stem cell transplants. Find out how a bone marrow transplant restores the bone ... autologous stem cell transplants and allogeneic stem cell transplants. ... marrows ability to create normal, hematopoietic stem cells. ... Borje S. Andersson, learn about the two types of stem cell ...
Allogeneic haematopoietic stem cell transplantation: individualized stem cell and immune therapy of cancer. Nat Rev Cancer 2010 ... and when targeting less immunogenic A20 tumor cells as well as a solid tumor RENCA (renal cell carcinoma; data not shown). ... Adoptive transfer of T-cell precursors enhances T-cell reconstitution after allogeneic hematopoietic stem cell transplantation ... Allogeneic hematopoietic stem cell transplantation (allo-HSCT) represents a potent therapy for malignant and nonmalignant ...
... versus-tumor response via allogeneic hematopoietic stem cell transplantation, and the administration of partially purified or ... effects in murine models have been linked to the direct killing of tumor cells by activated T cells and natural killer cells, ... Renal cell carcinoma evokes an immune response, which occasionally results in spontaneous and significant remissions (1 , 2) . ... responses were limited to patients with clear cell tumors with the favorable histologic patterns described in the primary tumor ...
Transplantation of HSC (HSCT) is done in order to re-establish bone marrow and immune system function after being damaged and/ ... TRANSPLANTATION? The term haematopoietic stem cell (HSC) refers to cells made in the blood factory or bone marrow that have the ... potential to grow into almost any type of blood cell. ... and allogeneic transplantation, where stem cells are obtained ... To this end, strategies to manipulate stem cells in order to shift the balance in favour of tumour -killing as well as the ...
Allogeneic Hematopoietic Stem Cell Transplantation Other: blood sample Detailed Description:. For both groups: 28ml of ... tumor and fœtal tolerance. They belong to innate immune cells but they have a link with adaptative immunity. Indeed, after some ... CMV reactivation is a major cause of morbidity and mortality after allogeneic hematopoietic ste cell transplantation in humans ... Study of Natural Killer Immunity During Infections With CMV or AdV After Allogeneic Hematopoietic Stem Cells. ...
... complications of allogeneic hematopoietic stem cell transplantation, and embryofetal toxicity.. Treatment of patients with ... and signaling through this pathway can contribute to inhibition of active T-cell tumor immune surveillance. In syngeneic mouse ... Binding of PD-L1 and PD-L2 to the programmed cell death protein 1 (PD-1) receptor found on T cells inhibits T-cell ... complications of allogeneic hematopoietic stem cell transplantation, and embryofetal toxicity. ...
Services include the processing of hematopoietic stem cells for autologous or allogeneic transplantation, generation of tumor ... vaccines using genetic or culture mediated modification of tumor cells, and preparation of immune cell populations for adoptive ... Tumor-specific immunotherapy components. Since most cell manipulation procedures are distinct and developmental, the cost of ... Tumor Imaging Metrics Core. The Tumor Imaging Metrics Core (TIMC) provides standardized, consistent, longitudinal radiological ...
Immune reconstitution after allogeneic hematopoietic stem cell transplantation in children: a single institution study of 59 ... and amplification of graft-versus-tumor effects by activated natural killer cells after allogeneic bone marrow transplantation ... Immune reconstitution after allogeneic stem cell transplantation: the impact of stem cell source and graft-versus-host disease ... 1 NK cells are of major importance in allogeneic hematopoietic stem cell transplantation (HSCT) because of their ability to ...
... cells are lymphocytes of innate immunity that respond to virus infected and tumor cells. After allogeneic transplantation, NK ... These adaptive NK cells display immune memory and methylation signatures like CD8 T cells. As potential therapy, NK cells, ... Strategies to activate NK cells to prevent relapse and induce remission following hematopoietic stem cell transplantation. ... Strategies to activate NK cells to prevent relapse and induce remission following hematopoietic stem cell transplantation. ...
Regulatory T (T,sub,reg,/sub,) cells play an important role in the enhanced graft-versus-tumor (GVT) effect and reduction of ... This review discusses the role of T,sub,reg,/sub, cells in a tumor-bearing mouse model treated with allo-HSCT + TT. ... Replacement and reduction of elevated T,sub,reg,/sub, cells by donor-derived allo-T,sub,reg,/sub, cells from the transplanted ... combined with thymus transplantation (TT) from the same donor (allo-HSCT + TT). This method induces elevated T cell function ...
NK cells are the most efficient effector cells of the innate immune system and have the capability to eliminate leukemic cells ... antigens on leukemic cells and seem to enhance T cell mediated antitumor activity by increasing tumor-specific CD8 T cell ... Allogeneic hematopoietic stem cell transplantation (HSCT) is a widely performed therapy for many hematologic malignancies. ... Progress in Hematology New immunotherapy-based approach in allogeneic hematopoietic stem cell transplantation. First Online: 19 ...
NSG mice are a proven host for engraftment of human tumors or establishment of human immunity following hematopoietic stem cell ... host for engraftment of human tumors or establishment of human immunity following hematopoietic stem cell transplantation. ... human immune cells and tumors is paramount when devising treatment strategies that prevent tumor evasion of immune cells and ... Evidence that humanized NSG™ and NSG™-SGM3 mice can support the growth of allogeneic human tumors ...
Transplantation of allogeneic hematopoietic stem cells: an emerging treatment modality for solid tumors. Nature Clin Pract ... Allogeneic Stem Cell Transplantation. Evidence of an immune-mediated effect against sarcoma in experimental animal models of ... of immune effector cells capable of tumor killing. This may be nonspecific, as in the case of allogeneic hematopoietic stem ... No improvement of survival with reduced- versus high-intensity conditioning for allogeneic stem cell transplants in Ewing tumor ...
ATG Based Conditioning Regimen in HLA Related HSCT for Aggressive T-cell Tumors ... ATG based conditioning regimen in HLA related allogeneic hematopoietic stem cell transplantation for aggressive T-cell tumors: ... the opsonophagocytic role of phagocytic cells and induced apoptosis(3). But some scholars reported the ATG delayed immune ... improve the outcome of allogeneic hematopoietic stem cell transplantation in patients with highly aggressive T-cell tumors. ...
... graft-versus-leukemia effect induced and maintained by donor T cells after allogeneic hematopoietic stem cell transplantation. ... T-cell receptor gene transfer exclusively to human CD8+ cells enhances tumor cell killing. Blood 2012;120:4334-42. ... The authors used multidimensional and multiplexed T-cell immune monitoring assays to longitudinally characterize the T cells of ... Moreover, parallel analyses may focus on cancer cells, B cells, natural killer cells, inflammatory cells, stromal cells, and ...
However, nivolumab had to be discontinued in one patient due to development of immune-related polyarthritis requiring treatment ... Our case series demonstrates that anti-PD-1 therapy with nivolumab can be highly effective following allogeneic transplant for ... Here, we report the outcomes of three patients with relapsed classical Hodgkins lymphoma following allogeneic transplant that ... Three patients with Hodgkins lymphoma relapsed following allogeneic transplant received nivolumab therapy at our institution. ...
... tumor-sensitive immune system by allogeneic hematopoietic stem cell transplantation (allo-HSCT). ... Stem cell product and stem cell transplantation. Only mobilized hematopoietic stem cells obtained from peripheral blood by ... Allogeneic hematopoietic stem cell transplantation in solid tumors. As the field of cancer immunology has grown, a deeper ... The STEM PACE trial is a single center, phase II study to evaluate adjuvant allogeneic hematopoietic stem cell transplantation ...
Development of tumor-reactive T cells after nonmyeloablative allogeneic hematopoietic stem cell transplant for chronic ... The induction of tumor immunity following allogeneic stem cell transplantation. Adv Immunol 2006;90:129-69. ... through analysis of B-cell responses in CLL patients with clinically evident tumor immunity but without anti-host immune ... Beyond HLA: the significance of genomic variation for allogeneic hematopoietic stem cell transplantation. Blood 2007;109:1355- ...
... to extend this strategy to allogeneic stem cell transplantation as well as the manipulation of cycling of primitive progenitors ... cells over neoplastic cells to achieve tumor-free autografts may ameliorate the results of autologous transplantation. The ... and the large scale production of professional antigen presenting cells capable of initiating the process of immune response. ... manipulation of hematopoietic stem/progenitor cells, cytotoxic effector cells and antigen presenting dendritic cells. ...
HLA-DRlow/neg IDO+ myeloid cells in patients following allogeneic hematopoietic stem cell transplantation. Leukemia 2013; 27(2 ... CD115+ immature myeloid suppressor cells mediate the development of tumor-induced T regulatory cells and T-cell anergy in tumor ... Suppressor Cells correlate with early infections and clinical outcomes in allogeneic hematopoietic stem cell transplantation. ... The Crosstalk between Myeloid Derived Suppressor Cells and immune cells: To establish immune tolerance in transplantation. J ...
... promises to extend the use of NK cells in cancer therapy beyond allogeneic mismatched hematopoietic stem cell transplantation. ... 1B). Reduced 2B4 expression in NK cells has been suggested to play a role in tumor immune escape (27). In our patients, the ... IL-2 activated NK cell immunotherapy of three children after haploidentical stem cell transplantation. Blood Cells Mol Dis 2004 ... NK cell-based immunotherapies have mostly focused on the haploidentical hematopoietic stem cell transplantation setting, where ...
  • By providing an overview of the immune biology of HSCT, an explanation of immune rejection, and detail on antigens and their role in HSCT success, this book embraces biologists and clinicians who need a broad view of the deeply complex processes involved. (
  • Hematopoietic stem cell transplantation (HSCT) or Bone marrow transplantation is a medical procedure in the field of hematology and oncology that involves transplantation of hematopoietic stem cells (HSC). (
  • Autologous HSCT involves isolation of HSC from a patient, storage of the stem cells in a freezer, high-dose chemotherapy to eradicate the malignant cell population at the cost of also eliminating the patient's bone marrow stem cells, then return of the patient's own stored stem cells to their body. (
  • Allogeneic HSCT involves two people, one is the (normal) donor and one is the (patient) recipient. (
  • Allogeneic hematopoietic stem cell transplantation (HSCT) is a very effective treatment for a number of hematological malignancies but relapse remains a major problem, especially in patients with high risk disease. (
  • Patients undergoing an allogeneic HSCT from a sibling donor, as treatment for a hematological malignancy. (
  • The purpose of this research study is to perform a serial analysis of immune function using blood cells and sera obtained from patients after vaccination following hematopoietic stem cell transplantation (HSCT). (
  • The focus of this study will be to characterize several immune parameters during the clinical course of HSCT and correlate these findings with the effect of vaccination. (
  • While innate immunity (myeloid and NK cell) is restored relatively quickly following HSCT, a prolonged period of lymphopenia occurs in all patients. (
  • In children who have received chemotherapy and HSCT, T cell function generally recovers within 6 to twelve months. (
  • There are many studies that correlate decreased T cell number and function (specifically CD4+ T cells) with an increase in post-transplant infections and relapse has been shown to be inversely proportional to T cell reconstitution following both autologous and allogeneic HSCT. (
  • Mature immunocompetent cells from the stem cell graft as well as early robust immune reconstitution are essential for the graft-vs. -tumor (GVT) effect to eliminate residual malignant cells after allogeneic hematopoietic stem cell transplantation (HSCT). (
  • Although allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment for various hematologic malignancies, it is still a procedure associated with a substantial risk of disease relapse and transplant-related morbidity and mortality (TRM) including graft-vs.-host disease (GVHD) ( 1 - 3 ). (
  • Transplantation of HSC (HSCT) is done in order to re-establish bone marrow and immune system function after being damaged and/or attacked by blood cancer. (
  • The most common indications for HSCT are blood cancers, mainly acute leukaemia, cancers of the lymphatic tissues (lymphomas) and the antibody-forming blood cells (multiple myeloma). (
  • HSCT can be broadly divided into autologous transplantation, where patients use their own blood stem cells, and allogeneic transplantation, where stem cells are obtained from a different person. (
  • The aim of this prospective study is to evaluate the role of NK cells, in particular NKG2C+ NK cells in the control of CMV but also Adenovirus after allo HSCT. (
  • We recently developed a new allogeneic hematopoietic stem cell transplantation method (allo-HSCT) combined with thymus transplantation (TT) from the same donor (allo-HSCT + TT). (
  • This method induces elevated T cell function with mild graft-versus-host disease (GVHD) in comparison to conventional HSCT alone and HSCT + donor lymphocyte infusion (DLI). (
  • This review discusses the role of T reg cells in a tumor-bearing mouse model treated with allo-HSCT + TT. (
  • The percentages of these cells in CD4 + T cells are intermediate between HSCT alone and HSCT + DLI, while the opposite is true for the percentage of CD4 + FoxP3 − effector T (T eff ) cells. (
  • We observed that not only the number of T cells but also the quantity of T cell receptor rearrangement excision circles (TREC) [ 8 ], which reflect production of T cells from the thymus, are increased in HSCT + TT. (
  • Malignant tumor-bearing mice treated with allo-HSCT + TT showed a strong graft-versus-tumor (GVT) effect but weak GVHD compared with HSCT alone and HSCT + DLI. (
  • This method makes use of intra-bone marrow-bone marrow transplantation (IBM-BMT) for HSCT, which involves the direct injection of HSC into the bone marrow cavity, and results in superior engraftment of donor cells and reduced incidence of GVHD with mesenchymal stem cells (MSC) [ 18 - 20 ]. (
  • In the case of conventional allo-HSCT, allo-HSC are transplanted into the host, and allo-T cells develop in the host thymus (Figure 1(a) ). (
  • Allogeneic hematopoietic stem cell transplantation (HSCT) is a widely performed therapy for many hematologic malignancies. (
  • Recent progress with various sources of hematopoietic stem cells has enabled many more candidates to receive HSCT and a number of patients have now survived for years posttransplant. (
  • In this review series, new immunotherapy-based approach in allogeneic HSCT, which are separating graft-versus-leukemia (GVL) effects and GVHD, are reviewed by experts. (
  • Regulatory T cells (Tregs) are pivotal for the maintenance of self-tolerance and tolerance induction after HSCT. (
  • will mainly focus on natural killer (NK) cell therapy after HSCT. (
  • In an experimental mouse model, NK cells have been shown to decrease GVHD after HSCT. (
  • Allogeneic hematopoietic (allo-HSCT) stem cell transplantation is an established treatment capable of to providing cure in a variety of hematopoietic malignancies. (
  • Allo-HSCT in advanced solid tumors including pancreatic cancer have been of limited success, however studies of allo-HSCT in solid tumors in minimal disease situations have never been performed. (
  • Study patients will undergo standard conditioning for allo-HSCT followed by transplantation of allogeneic unmanipulated peripheral blood stem cells. (
  • Although chronic lymphocytic leukemia (CLL) is most often controlled with combination chemotherapy ( 1 ), allogeneic hematopoietic stem cell transplantation (HSCT) remains the only potentially curative treatment for this disease ( 2 , 3 ). (
  • Rescue and intensive chemotherapies followed by autologous hematopoietic stem cell transplantation (auto-HSCT) can put into remission about half of the patients [ 4 ]. (
  • The subset of patients necessitating further treatment in the cases of second relapse or refractory disease is considered for allogeneic HSCT (allo-HSCT). (
  • Solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) recipients are vulnerable to a wide variety of infections: bacterial, fungal, viral or parasitic. (
  • Epstein-Barr virus (EBV) reactivation is an unresolved medical issue after allogeneic hematopoietic stem cell transplantation (HSCT). (
  • Hematopoietic stem cell transplantation (HSCT) has revolutionized the treatment of hematologic malignancies, bringing substantial improvements to survival outcomes for many patients. (
  • We provide an overview of these two immunotherapeutic strategies following HSCT, with discussions centered on NK and T-cell biology and contributions to the GVL effect as well as the current research directions in the field as related to adoptive cell therapy after HSCT. (
  • Allogeneic hematopoietic stem cell transplantation (HSCT) is a major therapy for malignant diseases of the blood and bone marrow and the most potent form of immune therapy against these diseases through its graft-versus-leukemia/tumor (GVL/GVT) effect. (
  • However, the efficacy of allogeneic HSCT has been impeded by frequent and severe graft-versus-host-disease (GVHD) that is tightly linked to the GVL/GVT effect. (
  • Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative treatment for many hematological malignancies resistant to other therapies. (
  • Using mouse models of allo-HSCT, we discovered that: 1) Notch-deprived donor T cells showed drastically reduced ability to produce effector cytokines (e.g. (
  • b PBMCs from a patient with chronic lymphocytic leukemia (CLL) before hematopoietic allogeneic stem cell transplantation ('pre-HSCT') (top) and following transplant ('post-HSCT') (bottom) were stimulated with CD40L-Tri-activated autologous CLL cells, and immunomagnetically selected CD8+ T cells were restimulated on ELISPOT assay with autologous CLL cells activated by the indicated CD40L formulation. (
  • Post-transplant lymphoproliferative disorders (PTLD) are a heterogeneous group of diseases occurring in the setting of transplantation of either hematopoietic stem cells (HSCT) or solid organs (SOT). (
  • recipients of allogeneic HSCT are at a particular risk for developing PTLD. (
  • The main application studied for CD34 enrichment as graft manipulation is allogeneic, and in particular, haploidentical hematopoietic stem cell transplantation (HSCT). (
  • Haploidentical HSCT can be a therapy option for patients suffering from haematologic malignancies or non-malignant diseases, who are eligible for allogeneic transplantation, and do not have a matched related or unrelated donor. (
  • HSCs) for therapeutic applications has been in development for Haematopoietic stem cell transplantation (HSCT) is a global y over 30 years, and two such treatments were recently granted accepted practice for the treatment of malignant and non-malignant market authorisation by the European Medicines Agency. (
  • HSCT is thus aimed at replenishing the bone marrow with stem cel s, up of seven years was shown for 18 study participants. (
  • Data from clinical rationale for HSCT is to provide the patient with a haematopoietic development show that patients treated with Zynteglo achieved either lineage that replaces or compensates for the underlying genetic complete transfusion independence or a near two-thirds reduction deficiency. (
  • Allogeneic HSCT, i.e. transplantation of HSCs harvested in the annual number and volume of blood transfusions. (
  • Our group is interested in understanding the biology of immune responses following allogeneic haematopoietic stem cell transplantation (allo-HSCT). (
  • Following allo-HSCT, activated donor T cells are recruited to peripheral organs where they cause severe injury, for example colitis or dermatitis. (
  • Together with Dr Clare Bennett, we have developed clinically relevant pre-clinical models of allo-HSCT permitting us to track evolving immune responses in considerable detail and at multiple sites. (
  • I am attending physician on the Bone Marrow Transplantation programme that runs at the Royal Free London and University College London Hospital, where I have a particular clinical interest in adoptive T cell therapy to prevent or treat relapse of leukaemia or lymphoma following allo-HSCT. (
  • He describes the evolution of his research, which has contributed significantly to advancing the field of gene transfer using retroviral vectors in the development of both autologous (AUTO) and allogeneic (ALLO) hematopoietic stem cell transplantation (HSCT) approaches to cancer immunotherapy, and the strategy of using chimeric antigen receptors (CARs) to modify T cells stimulating their activation, proliferation, and anti-tumor activity. (
  • After pursuing the development of cellular therapies to treat immune disorders, Dr. Brenner shifted the focus of his research to bone marrow transplantation, or what is now called HSCT. (
  • There is evidence from allogeneic hematopoietic stem cell transplantation [HSCT] that there is an immune response against leukemia-associated antigens in patients with either acute or chronic myeloid leukemia (AML, CML). (
  • In this novel study, we will employ the novel culture method to conduct a multi-center Phase 1/2 clinical trial of adoptive autologous T cell therapy in patients who have recently received an autologous HSCT (AHSCT) for AML. (
  • CMV infection (CMV-I) remains an important complication of hematopoietic stem cell transplantation (HSCT). (
  • These efforts are based on studies of patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) for hematologic malignancies. (
  • In patients undergoing HSCT, depleting donor marrow T cells with an antibody to a T cell surface structure results in a dramatic decrease in the incidence of GVHD. (
  • The investigators propose a nonrandomized, Phase I study to assess the safety of infusion of NK cells that will be selected from sibling donors and infused to patients with hematological malignancies early following allogeneic stem cell transplantation. (
  • Safety and Toxicity of Escalating Doses of Adoptively Infused ex Vivo Selected CD56+CD3- NK Cells on Day 7 Following Allogeneic Stem Cell Transplantation in Patients With Hematological Malignancies. (
  • To evaluate the safety and toxicity of escalating doses of ex vivo selected donor CD56+CD3- NK cells, adoptively infused on day 7 following sibling allogeneic stem cell transplantation in patients with hematological malignancies. (
  • Allogeneic hematopoietic stem cell transplantation and checkpoint blockade therapy are immune-based therapies that have activity in selected refractory hematologic malignancies. (
  • These advances make transplantation a viable treatment for many more patients with hematologic malignancies. (
  • Although T cells clearly participate in graft-versus-leukemia (GvL) responses ( 11 ), several studies have implicated an important role for B-cell immunity in remission of hematologic malignancies following transplant and DLI ( 12 - 14 ). (
  • Antigen-specific 2B4ζ-expressing NK cells may be a powerful new tool for adoptive immunotherapy of leukemia and other malignancies. (
  • Our data thus pave the way toward the clinical application of NK cells for the efficient and specific elimination of minimal residual tumor cells in various malignancies. (
  • However, complete quantitative and qualitative restoration of the T cell compartment may take many years, or in some cases may not fully recover, and is linked to increased infection, relapse, secondary malignancies, and overall mortality in transplant recipients ( 8 ). (
  • Hematological malignancies have long been at the forefront of the development of novel immune-based treatment strategies. (
  • In adoptive cell therapy these qualities are used to treat primary malignancies, life-threatening virus infections or leukemic relapses after allogeneic hematopoietic stem cell transplantation. (
  • We studied 113 consecutive patients with hematologic malignancies who received non-T-cell-depleted BMT from human leukocyte antigen (HLA)-matched siblings. (
  • Hematopoietic stem cell transplantation has revolutionized the treatment of hematologic malignancies, but infection, graft- versus -host disease and relapse are still important problems. (
  • These cancers comprise most non-Hodgkin's lymphomas, some leukemias, and myelomas, and are known collectively as B-cell malignancies. (
  • In the study, patients with B-cell malignancies after alloHSCT received a single infusion of donor CAR-T cells, with no chemotherapy or other therapies administered. (
  • The study, titled 'Allogeneic T Cells that Express an Anti-CD19 Chimeric Antigen Receptor Induce Remissions of B-Cell Malignancies that Progress After Allogeneic Hematopoietic Stem-Cell Transplantation Without Causing Graft-Versus-Host Disease,' was a phase 1 dose escalation trial carried out by the Experimental Transplantation and Immunology Branch of the National Cancer Institute (NCI) in partnership with JTCC. (
  • Relapse of hematologic malignancies is the primary cause of treatment failure after allogeneic hematopoietic stem cell transplantation (HCT). (
  • The Wilms' tumor 1 (WT1) gene product is a tumor-associated antigen that is expressed in acute leukemia and other hematologic malignancies, with limited expression in normal tissues. (
  • Indications for microtransplantation are as follows: Hematologic Malignancies Tumors Acute myeloid leukemia (AML) chronic-phase chronic myeloid leukemia (CP-CML) Myelodysplastic syndromes (MDS) Intermediate- or high-risk Non-Hodgkin lymphoma High-risk Hodgkin lymphoma Multiplemyeloma (MM) Severe aplastic anemia (SAA) The cells employed are allogeneic peripheral blood stem cells. (
  • In particular, he has focused on allogeneic stem cell transplantation and tumor immunology to treat aplastic anemia, hematological malignancies, and solid tumors. (
  • He and his colleagues are also developing methods to increase the expression of adhesion molecules on NK cells that will allow them to better access the bone marrow microenvironment where hematologic malignancies originate. (
  • Information gleaned from Dr. Childs's translational research has defined novel pathways through which malignancies may be targeted by the human immune system. (
  • Dr. Childs is also the Section Chief and Senior Investigator in the Laboratory of Transplantation Immunotherapy where his research focuses on allogeneic stem cell transplantation and tumor immunology to treat aplastic anemia, hematological malignancies, and solid tumors. (
  • Lymphoid malignancies typically promote an infiltrate of immune cells at sites involved by the disease. (
  • Patients with hematologic and lymphoid malignancies can benefit greatly from allogeneic hematopoietic stem cell transplantation (alloHSCT), achieving long-term cures in many cases but too often at the expense of graft-versus-host disease (GvHD). (
  • 3. Gill S. Planes, trains, and automobiles: perspectives on CAR T cells and other cellular therapies for hematologic malignancies. (
  • Genetically modified T-cell-based adoptive immunotherapy in hematological malignancies. (
  • 11. Okroj M, Osterborg A, Blom AM. Effector mechanisms of anti-CD20 monoclonal antibodies in B cell malignancies. (
  • 12. Safdari Y, Ahmadzadeh V, Farajnia S. CD20-targeting in B-cell malignancies: novel prospects for antibodies and combination therapies. (
  • B-cell receptor signaling in chronic lymphocytic leukemia and other B-cell malignancies. (
  • Hematopoietic stem cell transplantation (HCT) is a potentially curative procedure for patients with hematologic malignancies who are otherwise incurable with conventional therapies. (
  • He is currently chief of the Division of Hematologic Malignancies and codirector of the Adult Stem Cell Transplantation Program. (
  • The second edition is fully revised and includes new chapters on microbiome, metabolism, kinase targets, micro-RNA and mRNA regulatory mechanisms, signaling pathways in GVHD, innate lymphoid system development, recovery and function in GVHD, genetically engineered T-cell therapies, immune system engagers for GVHD and graft-versus-tumor, and hematopoietic cell transplant for tolerance induction in solid organ grafts. (
  • Children or adults with aplastic anemia have lost their stem cells after birth and may not require such high doses of chemotherapy and irradiation prior to a transplant. (
  • Allogeneic transplant donors may be related (usually a sibling) or unrelated volunteers. (
  • These long-lasting T cell deficiencies have been shown to play a direct role in post-transplant complications. (
  • Furthermore, this prolonged deficit in T cell function decreases the effectiveness of vaccination against tumour antigens and infectious diseases as well as other post-transplant immunotherapeutic strategies. (
  • A stem cell transplant is often the best option to treat blood cancers, such as leukemia , lymphoma and multiple myeloma , as well as bone marrow failure syndromes like myelodysplastic syndrome . (
  • A hematopoietic stem cell transplant replaces faulty cells so the body can produce normal, healthy cells again. (
  • An autologous stem cell transplant uses the patient's own cells for treatment. (
  • An allogeneic stem cell transplant is similar, but we take cells from someone other than the patient. (
  • Where do allogeneic stem cell transplant donor cells come from? (
  • With a peripheral blood cell transplant, the donor receives growth factor shots to stimulate the bone marrow to push the stem cells into the blood. (
  • The cells for a cord blood transplant come from an umbilical cord collected at birth by the MD Anderson Cord Blood Bank . (
  • NK cells are the first lymphocytes that return to normal concentrations post-transplant ( 15 ), and separate studies report improved clinical outcomes of both high graft doses ( 16 , 17 ) and robust immune reconstitution ( 14 , 18 ) of NK cells. (
  • In the case of allogeneic transplant, the patient's donor will also have to undergo an assessment. (
  • Dominant in the NK cell transplant literature are killer cell immunoglobulin-like receptors (KIR), encoded on chromosome 19q. (
  • Allogeneic transplant donors having a KIR B haplotype and lacking a recipient HLA-C epitope provide protection against relapse from acute myeloid leukemia (AML). (
  • Polyclonal antithymocyte globulin (rabbit anti-thymocyte globulin, r-ATG) are currently used to prevent graft-versus -host(GVHD) disease in allogeneic stem cell transplantation, and also widely used for the prevention and treatment of acute rejection after solid organ transplant because of its strong immunomodulatory effects. (
  • Here, we report the outcomes of three patients with relapsed classical Hodgkin's lymphoma following allogeneic transplant that were treated with the anti-PD-1 antibody, nivolumab. (
  • Three patients with Hodgkin's lymphoma relapsed following allogeneic transplant received nivolumab therapy at our institution. (
  • Our case series demonstrates that anti-PD-1 therapy with nivolumab can be highly effective following allogeneic transplant for Hodgkin's lymphoma, but serious immune-related adverse events can occur, requiring very close monitoring and interruption of therapy. (
  • At the forefront of research to increase access to hematopoietic stem cell transplantation and improve outcomes, the Center has amassed a clinical database containing information on nearly 350,000 transplant recipients. (
  • How would you characterize the current status of hematopoietic stem cell transplant? (
  • They also allow us to consider transplantation in other disorders where high transplant-related mortality rates were previously considered prohibitive-for example, in people with severe sickle cell disease or autoimmune disease. (
  • What are the main barriers to successful hematopoietic stem cell transplant today, and what will it take to overcome them? (
  • A lot of effort really needs to be devoted to addressing why some patients are cured and others are not after autologous transplant and allogeneic transplant-the answer might differ for those two approaches-and what can we do about it. (
  • Patients with chronic lymphocytic leukemia (CLL) who relapse after allogeneic transplant may achieve durable remission following donor lymphocyte infusion (DLI), showing the potency of donor-derived immunity in eradicating tumors. (
  • Clearly, this more diverse view of the genome has significant implications for allogeneic hematopoietic stem cell transplantation, not least in the generation of transplant antigens but also in terms of individual susceptibility to transplant-related toxicities. (
  • The thymus plays a key role post allogeneic hematopoietic stem cell transplantation in the generation of a broad but self-tolerant T cell repertoire, but it is exquisitely sensitive to a range of insults during the transplant period, including conditioning regimens, corticosteroids, infections, and graft-versus-host disease. (
  • Such regenerative strategies may ultimately enable the thymus to play as prominent a role after transplant as it once did in early childhood, allowing a more complete restoration of the T cell compartment. (
  • However, major challenges persist, including overcoming the hurdle of prolonged post-transplant immunodeficiency through successful immune reconstitution ( 2 ). (
  • In the early post-transplant period, there is peripheral expansion of adoptively transferred donor T cells in the graft or recipient T cells that survive conditioning. (
  • Cytotoxic T cells (T C cells, CTLs, T-killer cells, killer T cells) destroy virus-infected cells and tumor cells, and are also implicated in transplant rejection. (
  • The study, published this week in the Journal of Clinical Oncology , demonstrates that infusing a transplant donor's T-cells, genetically modified to express a chimeric antigen receptor (CAR) targeting an antigen known as CD19, can induce complete or partial remission of certain blood cancers in patients who have previously received an allogeneic hematopoietic stem cell transplantation (alloHSCT). (
  • However this approach also impairs beneficial regulatory T cells (Treg) required for immune tolerance and cytotoxic T lymphocytes (CTL) that mediated the anti-tumor activity of the transplant. (
  • Donor's stem cells, which have been processed, will also accelerate functional recovery of recipient's hematopoietic stem cells, greatly reducing infections and transplant-related mortality. (
  • Upon infusion of the CD56-enriched CD3-positive donor lymphocytes, these cells may facilitate the reconstitution of CD4-positive T cells, regulatory T cells (Tregs) and natural killer (NK) cells, which may reduce the incidence of post-transplant graft-versus-host disease (GvHD) following haploidentical stem cell transplant (SCT). (
  • Epstein-Barr virus-related post-transplant lymphoproliferative disorders are recognized as a significant cause of morbidity and mortality in patients undergoing hematopoietic stem cell transplantation. (
  • To better define current understanding of post-transplant lymphoproliferative disorders in stem cell transplant patients, and to improve its diagnosis and management, a working group of the Sixth European Conference on Infections in Leukemia 2015 reviewed the literature, graded the available quality of evidence, and developed evidence-based recommendations for diagnosis, prevention, prophylaxis and therapy of post-transplant lymphoproliferative disorders exclusively in the stem cell transplant setting. (
  • Current Research and Scholarly Interests My research interest is on immunotherapy (including allogeneic transplant) of cancer. (
  • I am also interested in using tumor vaccine along with hematopoietic cell transplant. (
  • A thorough T and B cell depletion is necessary to reduce the risk of severe graft-versus-host disease (GvHD) and post-transplant lymphoproliferative disorders (PTLD). (
  • Together with colleagues he developed and tested an approach to improve patients' immune recovery after their T cells are depleted in preparation for a transplant. (
  • She received the successful bone marrow transplant she needed, but her immune system became severely depleted. (
  • Today, the Amy Strelzer Manasevit Research Program for the study of post-transplant complications is one of the largest and most coveted fellowships in the field of transplantation. (
  • This includes immune suppression associated with organ transplant (from the drugs taken to prevent organ rejection) and with HIV/AIDS infection. (
  • Bone marrow transplantation, or allogeneic hematopoietic stem cell transplant (HCT), is the only curative therapy for many patients with leukemia. (
  • Salvage second allogeneic stem cell transplantation (alloSCT2) is limited by high rates of transplant. (
  • Dr. Soiffer is chairman of the Center for International Blood and Marrow Transplant Research advisory committee and has served as vice president (2006), president (2007), and immediate past president (2008) of the American Society of Blood and Marrow Transplantation. (
  • Although allogeneic transplantation can cure a proportion of these individuals, success is limited by transplant-related complications such as graft-versus-host disease (GVHD). (
  • We are exploring the role of regulatory T cells (Tregs) in the development of GVHD and GVL reactions, and have initiated a clinical trial to augment GVL reactivity using an antibody to CTLA4Ig, a molecule that controls immune reactions.We are also investigating vaccination strategies for preventing relapse in allogeneic transplant patients. (
  • As assessed by blinded independent central review using Response Evaluation Criteria in Solid Tumors, version 1.1, median progression-free survival was 15.1 months vs 11.1 months (HR = 0.69, P = .0001). (
  • Immunotherapy has long been discussed as a promising method for the treatment of patients with solid tumors but thus far its exact role in sarcoma remains to be defined. (
  • secondary and exploratory endpoints included overall survival (OS), objective response rate (ORR), progression-free survival (PFS) and time to progression (TTP) using modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria. (
  • On May 23, 2017 , pembrolizumab (Keytruda) was granted accelerated approval for treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors progressing following prior treatment and who have no satisfactory alternative treatment options or with MSI-H or dMMR colorectal cancer progressing following treatment with fluoropyrimidine, oxaliplatin, and irinotecan. (
  • and 84% of those with metastatic colorectal cancer and 53% of those with other solid tumors had received at least 2 prior lines of therapy. (
  • Pubmed ID: 18422754 CML66 is a newly identified differentiation antigen that is expressed broadly in human leukemia and solid tumors, but its physiological function remains unknown. (
  • Evaluation Criteria in Solid Tumors (RECIST) v1.1, modified to follow a maximum of 10 target lesions and a maximum of five target lesions per organ. (
  • Among the patients with SCLC enrolled in KEYNOTE-158 (cohort G) (n=107) and KEYNOTE-028 (cohort C1) (n=24) who were included in the safety analysis, the adverse reactions that occurred were similar to those occurring in patients with other solid tumors who received KEYTRUDA as a single agent. (
  • Autologous applications make sense in the treatment of aplastic anemia, bone marrow cancers (e.g. plasma cell leukemia, Waldenström's macroglobulinemia) or solid tumors (e.g. retinoblastoma) or metabolic disorders. (
  • Uses antigens (markers on cells) to specifically target cells that express the marker, including cancer cells, with therapeutic agents. (
  • Chapter 7 - Tumor-Associated Antigens. (
  • To avoid rejection of the transplanted stem cells or severe graft-versus-host disease , the donor should have the same human leukocyte antigens (HLA) as the recipient. (
  • Nonetheless, tumor-cells evade the specific T-lymphocyte mediated immune surveillance using many mechanisms but especially by the down-regulation of the expression of HLA class I antigens. (
  • Peripheral expansion of T cells in a lymphopenic setting leads to a narrowing of the TCR repertoire and manifests as a decrease in the magnitude of response to new antigens. (
  • We all have protein structures called human leukocyte antigens (HLA) on our cells' surfaces. (
  • HMA have shown to upregulate several antigens on leukemic cells and seem to enhance T cell mediated antitumor activity by increasing tumor-specific CD8 T cell responses against these upregulated antigens. (
  • Clinical application has become possible thanks to the cloning of human TCRs specific for tumor antigens and technologies for the insertion of TCR-α and -β chain genes into human lymphocytes. (
  • Along with additional candidate antigens DAPK3, SERBP1, and OGFOD1, these proteins showed higher transcript and protein expression in B cells and CLL cells compared with normal peripheral blood mononuclear cells. (
  • DAPK3 and the shared antigens do not represent minor histocompatibility antigens, as their sequences are identical in both donor and tumor. (
  • These B-cell antigens represent promising biomarkers of effective anti-CLL immunity. (
  • Some B-cell-defined antigens ( 15 ) have been shown to elicit T-cell responses, and effective tumor immunity likely comprises a coordinated humoral and cellular adaptive immune response. (
  • In the current study, we identify several novel candidate antigens through analysis of B-cell responses in CLL patients with clinically evident tumor immunity but without anti-host immune reactions following DLI. (
  • Potential uses of these antigens include immune monitoring of CLL following therapy and even as immunogens for CLL-specific vaccines. (
  • Inhibitory receptors [e.g., killer immunoglobulin receptors (KIR)] interact with self-MHC class I antigens and protect normal cells from NK cell attack. (
  • Many malignant cells express MHC class I antigens and are thus naturally resistant to lysis by autologous NK cells. (
  • At the heart of the specificity of these novel strategies is the recognition of target antigens presented by malignant cells to T cells. (
  • Antigens are markers on cells that can be used to specifically target cells that express the marker and, specifically, tumor antigens are those present on cancer cells but not normal cells. (
  • However, tumor-specific antigens are rare, as most antigens that are expressed by malignant cells are also found in normal tissues, therefore the more accurate designation of these antigens is "tumor-associated antigens (TAA)", rather than tumor-specific. (
  • Specialized gamma delta T cells , (a small minority of T cells in the human body , more frequent in ruminants ), have invariant T-cell receptors with limited diversity, that can effectively present antigens to other T cells [3] and are considered to be part of the innate immune system . (
  • Helper T cells become activated when they are presented with peptide antigens by MHC class II molecules, which are expressed on the surface of antigen-presenting cells (APCs). (
  • This contrasts with MHC class II molecules's antigens which are peptides derived from phagocytosis/endocytosis and molecular degradation of non-self entities' proteins, usually by antigen-presenting cells. (
  • MiHA antigens are either ubiquitously expressed in most tissue like skin and intestines or restrictively expressed in the immune cells. (
  • Although graft or bone marrow rejection can have detrimental effects, there are immunotherapy benefits when cytotoxic T lymphocytes are specific for a self antigen and can target antigens expressed selectively on leukemic cells in order to destroy these tumor cells referred to as graft-versus- leukemia effect (GVL). (
  • Some of these antigens are ubiquitously expressed in nucleated male cells, and the presence of these antigens has been associated with a greater risk of developing GVHD allogeneic stem cell transplantation for a HLA matched gene when there's a male recipient and female donor. (
  • Their task is to take up, process and present antigens on their cell surface, which enables them to activate antigen-specific T cells for maturation and proliferation. (
  • CD47 blockade by use of a high affinity SIRP α variant protein (CV1) has been shown to improve the effects of monoclonal antibodies to high-density antigens in tumor models by enhancement of antibody dependent cellular phagocytosis (ADCP). (
  • As the minor histocompatibility antigens (mHAgs) play a dual role in the GvL and GvHD, the reconstitution of male-specific mHags (HY)-specific T cells were monitored. (
  • The laboratory continues to identify antigens that are derived from the endogenous retrovirus that may serve as a target for T-cell immunotherapy. (
  • ref. 2 ) facilitated induction of strong and durable tolerance by T cells to specific alloantigens, without disrupting protective responses to third-party antigens ( 3 ). (
  • Graft-versus-host disease (GVHD) is a major clinical problem and is caused by donor T cells within the graft that recognize antigens found in the patient but not the donor. (
  • T cells specifically bind particular tumor-associated molecules (antigens) and kill bound cancer cells through proteins called "T cell receptors" (TCRs). (
  • The results suggest a protective effect of high doses of NK cells in grafts and during early immune reconstitution and support the perception of NK cells as innate effector cells with anti-tumor effects in the setting of allogeneic stem cell transplantation. (
  • The selective production of cellular subsets to manipulate the graft versus-host and graft versus-tumor effects and anti-tumor vaccination strategies may be important to improve cellular adoptive immunotherapy. (
  • Indeed, the anti-tumor effect of these cytoablative strategies is believed to be caused not only by direct effects on the malignant cells, but also in part by induction of new T cell responses, as T cells expand within the lymphopenic environment ( 9 ). (
  • A major challenge is to select and prepare cells that mediate anti-tumor effects without causing life-threatening side effects such as graft versus host disease. (
  • The methods of the disclosure induce a systemic allogeneic anti-tumor immune response that results in tumor regression in untreated sites of disease, i.e. non-injected, non-irradiated, etc. (
  • 2. The method of claim 1, wherein said allogeneic anti-tumor T cell immune response further comprises at least about 5% circulating allogeneic type CD3 + T cells. (
  • The technology, B-I09, is a small molecule inhibitor of XBP-1 that acts as an immunotherapeutic agent which regulates DC response to inflammatory stimuli, preventing acute GVHD in DC-allostimulated human T cells, while maintaining Treg function and anti-tumor activity by CTLs and NK cells. (
  • Research in novel immunotherapies to treat acute myeloid leukemia is focused on enhancing antitumor specific anti-tumor immunity via vaccination or adoptive cell transfer (ACT) or antibody-based targeting of the tumoral microenvironment. (
  • In addition, blocking CD47 signaling activates both an anti-tumor cytotoxic T-lymphocyte (CTL) immune response and T-cell-mediated killing of CD47-expressing tumor cells. (
  • This beneficial anti-tumor activity largely derives from infused donor T cells, named graft-versus-tumor (GVT) effect. (
  • However, an autologous anti-tumor cell response in AML is either not evident or actively suppressed due to replacement of the lymphohematopoietic space with rapidly growing malignant cells. (
  • The ideal antigen is present on cancer cells but not on normal cells. (
  • NK cells are identified by the expression of the CD56 surface antigen and the lack of CD3. (
  • Strategies combining NK cell infusions with CD16-binding antibodies or immune engagers could make NK cells antigen specific. (
  • In the 1970s and 1980s, identification of the principles of antigen-specific T-cell reactivity led to the discovery of the T-cell receptor (TCR) and its cognate antigen, peptide presented by MHC (HLA in humans). (
  • This receptor-ligand pair guides cellular antigen specificity of the immune system. (
  • Moreover, these animals serve as a unique source of donor T cells that can be used to study virtually any property of antigen-specific T cells relevant for immunity upon adoptive transfer in recipient mice with infections or tumors. (
  • This is particularly true in the area of allogeneic transplantation, where the major barriers to widespread use were the toxicity associated with high-dose chemotherapy and radiation given beforehand, and the high risk of graft-vs-host disease, especially when using donors other than human leukocyte antigen (HLA)-identical siblings. (
  • Furthermore, we may be able to use immune therapy in the autologous setting, perhaps with vaccination strategies or with genetically altered immune cells (ie, chimeric antigen receptors) that target residual cancer. (
  • The present review covers three major area of interest in experimental and clinical hematology: manipulation of hematopoietic stem/progenitor cells, cytotoxic effector cells and antigen presenting dendritic cells. (
  • Concurrently, other important potential applications for ex vivo manipulation of hematopoietic cells have recently been investigated such as the generation and expansion of cytotoxic cells for cancer immunotherapy, and the large scale production of professional antigen presenting cells capable of initiating the process of immune response. (
  • Altered recognition of antigen is a mechanism of CD8+ T cell tolerance in cancer. (
  • Integration of the 2B4 endodomain into T-cell receptor ζ chimeric receptors significantly enhanced all aspects of the NK cell activation response to antigen-expressing leukemia or neuroblastoma cells, including CD25 up-regulation, secretion of IFN-γ and tumor necrosis factor-α, release of cytolytic granules, and growth inhibition, and overcame NK cell resistance of autologous leukemia cells while maintaining antigen specificity. (
  • Besides antigen-specific CTLs, cellular components of the innate immune system can contribute to immune surveillance of malignant cell growth. (
  • The ideal tumor antigen would be a "tumor-specific antigen", which is one that is expressed solely by malignant cells, thereby providing a unique target that will lead to maximal tumor elimination with minimal off-target toxicity. (
  • These cells recognize their targets by binding to antigen associated with MHC class I molecules, which are present on the surface of all nucleated cells. (
  • Antigen-naïve T cells expand and differentiate into memory and effector T cells after they encounter their cognate antigen within the context of an MHC molecule on the surface of a professional antigen presenting cell (e.g. a dendritic cell). (
  • The single unifying theme for all memory T cell subtypes is that they are long-lived and can quickly expand to large numbers of effector T cells upon re-exposure to their cognate antigen. (
  • Other Name: CBM.BCMA Chimeric Antigen Receptor T cell. (
  • Bio Rad ( The T Cell Marker, CD3 Antigen and Antibodies, 2016). (
  • Recognition of self-human leukocyte antigen (HLA) class I molecules by inhibitory killer cell immunoglobulin-like receptors (KIRs) is involved in the calibration of NK cell effector capacities during the developmental stage, allowing the subsequent recognition and elimination of target cells with decreased expression of self-HLA class I (due to virus infection or tumor transformation) or HLA class I disparities (in the setting of allogeneic transplantation). (
  • Adenovirus-specific CD4+ T cell clones recognizing endogenous antigen inhibit viral replication in vitro through cognate interaction. (
  • The lack of recognition of a T cell to this self antigen is the reason why allogeneic stem cell transplantation for an HLA matched gene or a developing fetus's MiHAs during pregnancy may not be recognized by T cells and marked as foreign leading to an immune response. (
  • The recognition of a mature T cell to this self antigen should not induce an immune response. (
  • Microtransplantation(MST) is an advanced technology to treat malignant hematological diseases and tumors by infusing patients with granulocyte colony-stimulating factor (G-CSF) mobilized human leukocyte antigen (HLA)-mismatched allogeneic peripheral blood stem cells following a reduced-intensity chemotherapy or targeted therapy. (
  • Dendritic cells (DCs) are the most potent antigen-presenting cells of our immune system. (
  • A proprietary agent that targets the cancer stem cell (CSC) antigen CD44, with potential antineoplastic activity. (
  • A variant of signal regulatory protein alpha (SIRPa) that antagonizes the human cell surface antigen CD47, with potential phagocytosis-inducing, immunostimulating and antineoplastic activities. (
  • CD47, also called integrin-associated protein (IAP), is a tumor-associated antigen (TAA) expressed on normal, healthy hematopoietic stem cells (HSC) and overexpressed on the surface of a variety of cancer cells. (
  • Transfer of Flt3L-induced Dll4+DCs that were loaded with tumor antigen-peptide induced potent CD8+ T cell-mediated antitumor activity. (
  • Identification of an Epitope Derived from CML66, a Novel Tumor-associated Antigen Expressed Broadly in Human Leukemia, Recognized by Human Leukocyte Antigen-A*2402-restricted Cytotoxic T Lymphocytes Cancer Science. (
  • Conversely, frequencies of T-cell populations were similar to those seen in healthy controls, and cytotoxic T-cells demonstrated antigen-specific activity after vaccination. (
  • We demonstrate that CD40L-Tri significantly expands normal CD19+ B cells by over 20- to 30-fold over 14 days and induces B cells to become highly immunostimulatory antigen-presenting cells (APCs). (
  • Consistent with these results, CD40L-Tri-activated B cells could effectively stimulate antigen-specific T responses (against the influenza M1 peptide) from normal volunteers. (
  • Together, our studies demonstrate the potent immune-stimulatory effects of CD40L-Tri on B cells that enable their expansion of antigen-specific human T cells. (
  • The development of methods to stimulate and monitor immunity against these leukemia cells, however, has been impaired by the poor antigen-presenting ability of CLL cells due to their low expression of costimulatory molecules. (
  • Clinical approaches currently used include allogeneic haematopoietic stem cell transplantation, chimeric antigen receptor T cell therapy and immune checkpoint inhibitors. (
  • However, in some specialised cell types, genome rearrangements must occur as programmed, highly orchestrated events, where they function to bring about genetic diversity: the B and T lymphocytes of our immune systems deliberately induce and repair DNA breaks in a mutagenic fashion to diversify antibody and antigen receptor encoding genes. (
  • Finally, the immunologically favorable environment created after ASCT may also represent an opportunity for approaches utilizing bispecific antibodies or chimeric antigen receptor (CAR) T cells. (
  • In particular, we are interested in how the mode of antigen presentation by different cells and tissues influences the type of immunity that is elicited. (
  • Durable remissions with BCMA-specific chimeric antigen receptor (CAR)-modified T cells in patients with refractory/relapsed multiple myeloma. (
  • This culture induces potent antigen presentation by inducing dendritic cell differentiation in the presence of autologous lymphocytes. (
  • Because even high doses of irradiation or chemotherapy cannot eradicate all malignant cells in all patients, ever more intensive conditioning regimens dominated efforts in clinical marrow transplantation until the late 1990s. (
  • In contrast to traditional allogeneic stem cell transplantation, in which the patient receives myeloablative conditioning (chemotherapy and/or irradiation), in NST, if donor cells are not infused or are rejected, the recipient's own bone marrow usually recovers spontaneously. (
  • We extract blood cells, treat the cancer with high-dose chemotherapy , then place the cells back into the patient. (
  • Once the cancer is less active and the patient has been pre-treated with chemotherapy (known as conditioning), he or she receives the donor's healthy stem cells. (
  • The rationale underlying autologous transplantation is to deliver high doses of chemotherapy (with or without radiotherapy). (
  • Whereas anti-tumour effects rely solely on high-doses of chemotherapy in autologous transplants, allogeneic HSC may also have beneficial immune activity that kills tumour/leukaemia. (
  • Screened eligible patients after surgical resection and standard adjuvant chemotherapy with HLA matched related stem cell donor can participate. (
  • Preliminary data demonstrate the possibility of using, in a clinical setting, ex vivo expanded hematopoietic cells with the aim of reducting, and perhaps abrogating, the myelosuppression after high-dose chemotherapy. (
  • It is important to note that much of the ensuing discussion may also have relevance to patients undergoing standalone chemotherapy or autologous HCT (auto-HCT), both of which can impart a degree of T cell depletion with thymic damage. (
  • However, unlike chemotherapy or auto-HCT, the strategy of allo-HCT is fundamentally based upon utilizing the beneficial effect of donor T cells, and we believe therapies to improve T cell reconstitution will be especially beneficial in this area. (
  • An interim analysis conducted by the independent Data Monitoring Committee (DMC) demonstrated that treatment with KEYTRUDA resulted in significantly longer OS than platinum-based chemotherapy (carboplatin plus paclitaxel or carboplatin plus pemetrexed) in patients with a PD-L1 tumor proportion score (TPS) of ≥1 percent. (
  • With KEYNOTE-042, KEYTRUDA has now shown a significant survival benefit compared with chemotherapy for patients with locally advanced or metastatic nonsquamous or squamous NSCLC expressing PD-L1 at 1 percent or higher by tumor proportion score," said Dr. Roger M. Perlmutter, president, Merck Research Laboratories. (
  • Chemotherapy is the treatment of cancer with drugs ("anticancer drugs") that can destroy cancer cells. (
  • In current usage, the term "chemotherapy" usually refers to cytotoxic drugs which affect rapidly dividing cells in general, in contrast with targeted therapy (see below). (
  • Chemotherapy drugs interfere with cell division in various possible ways, e.g. with the duplication of DNA or the separation of newly formed chromosomes. (
  • Most forms of chemotherapy target all rapidly dividing cells and are not specific for cancer cells, although some degree of specificity may come from the inability of many cancer cells to repair DNA damage, while normal cells generally can. (
  • The study will include the following sequential phases: Screening, Pre- Treatment (Cell Product Preparation, Lymphodepleting Chemotherapy), C-CAR088 infusion and Follow-up. (
  • RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. (
  • Differentiating this study from other CAR-T cell studies was the fact that chemotherapy was not administered prior to infusion. (
  • and chemotherapy and radiotherapy can have a negative effect on normal cells. (
  • Giving chemotherapy earlier allows oncologists to evaluate the effectiveness of the therapy, and may make removal of the tumor easier. (
  • In the hematopoietic cell transplantation field, T cells play a major role in the GVL effect, which can eradicate tumor cells in patients who resist chemotherapy. (
  • Chemotherapy is used by lower doses only to destroy cancer and partially suppress patient's immune system, which will be reinitiated by donor's stem cells soon after transplantation, and will play a role as recipient-versus-tumor (RVT) effect combining donor cells' graft-versus-tumor (GVT) effect. (
  • To overcome the intolerable severe reactions of high-dose chemotherapy and GVHD, as well as the challenge to find HLA-matched donors for conventional hematopoietic stem cell transplantation, Dr Huisheng Ai, Guo Mei, etc. developed a new regimen of reduced-intensity chemotherapy plus G-CSF mobilized HLA-mismatched allogeneic peripheral blood stem cell infusion, which was firstly employed for a 75-year-old patient in 2002 and later named as Microtransplantation. (
  • Study design: Medigene's Phase I/II trial (NCT02405338) will include 20 AML patients who show complete remission after standard chemotherapy but are not eligible for stem cell transplantation that would reduce the risk of a relapse. (
  • For these patients', besides chemotherapy, treatment with brentuximab vedotin, PD-1 inhibitors, autologous or allogeneic hematopoietic stem cell transplantation, or participation in clinical trial comprise potential therapy options. (
  • Changes in adaptive immune cells after chemotherapy in adult acute myeloid leukemia (AML) may have implications for the success of immunotherapy. (
  • This study was designed to determine the functional capacity of the immune system in adult patients with AML who have completed chemotherapy and are potential candidates for immunotherapy. (
  • We used the response to seasonal influenza vaccination as a surrogate for the robustness of the immune system in 10 AML patients in a complete remission post-chemotherapy and performed genetic, phenotypic, and functional characterization of adaptive immune cell subsets. (
  • Effector T-cells had increased PD-1 expression in AML patients least removed from chemotherapy. (
  • The observed B-cell abnormalities may explain the poor response to vaccination often seen in AML patients after chemotherapy. (
  • Furthermore, the uncoupled recovery of B-cell and T-cell immunity and increased PD-1 expression shortly after chemotherapy might have implications for the success of several modalities of immunotherapy. (
  • Though immunotherapeutic strategies to maintain remission after patients receive intensive chemotherapy are logical and being tested in clinical trials [ 6 ], there is an incomplete description of the state of the adaptive immune system in AML patients who have completed chemotherapy. (
  • Yet, the functional capacity of the immune system in AML patients after the completion of intensive chemotherapy is largely unknown, and this has important implications for the success of any subsequent immunotherapy intended to prevent relapse, especially cancer vaccination and immune checkpoint blockade meant to augment endogenous cellular-mediated anti-leukemic responses. (
  • 4,5] For these cases, rare primary immune disorder, known as adenosine deaminase- patients initial y receive a chemotherapy regimen to destroy tumour deficient severe combined immunodeficiency (ADA-SCID). (
  • In the study supporting this approval, KEYTRUDA in combination with paclitaxel, nab-paclitaxel or gemcitabine and carboplatin significantly improved progression-free survival for patients with advanced triple-negative breast cancer whose tumors express PD-L1 with CPS greater than or equal to 10 compared with the same chemotherapy regimens alone. (
  • The accelerated approval was based on data from KEYNOTE-355 ( , NCT02819518 ), a multicenter, double-blind, randomized, placebo-controlled trial conducted in 847 patients with locally recurrent unresectable or metastatic TNBC, regardless of tumor PD-L1 expression, who had not been previously treated with chemotherapy in the metastatic setting. (
  • It is necessary to apply them in the oncological treatment process after high-dose chemotherapy in order to restore the hematopoietic and immune system. (
  • These cells usually repair themselves after chemotherapy. (
  • RATIONALE: Peripheral stem cell transplantation may allow doctors to give higher doses of chemotherapy drugs and kill more cancer cells. (
  • Combining chemotherapy with allogeneic or autologous peripheral ste. (
  • Salvage chemotherapy induces disease remissions in patients with relapsed or refractory (r/r) T-cell lymphomas, but fails to provide lasting tumor control. (
  • NK role in tumor-cells clearance is proved by allogenic stem cells transplantation, since a better engraftment and a low relapse rate are observed when the graft NK inhibitory receptors mismatch with recipient HLA molecules ( 3 ) (Figure 1 ). (
  • The importance of this effect was demonstrated by an increased rate of leukemia relapse in patients receiving transplants in which identical twin donors were used or T cell depletion of donor marrow was performed ( 5 ). (
  • Patients transplanted with graft NK cell doses above the median value of 27 × 10 6 /kg had significantly increased relapse-free-survival compared to patients transplanted with lower doses, HR 2.12 (95% CI 1.01-4.45, p = 0.04) Peripheral blood concentrations of NK cells obtained from donors before G-CSF mobilization were significantly correlated to graft NK cell doses (Spearman's ρ 0.53, p = 0.03). (
  • Early immune reconstitution above median values of NK cells was significantly associated with improved relapse-free survival (HR 2.84 [95% CI 1.29-6.28], p = 0.01, and HR 4.19 [95% CI 1.68-10.4], p = 0.002, for day 28 and 56, respectively). (
  • Early concentrations above the median value of the mature effector CD56dim NK cell subset were significantly associated with decreased relapse incidences at 1 year, 7% (95% CI 1.8-17) vs. 28% (95% CI 15-42), p = 0.04, and 7% (95% CI 1.8-18) vs. 26% (95% CI 14-40) %, p = 0.03, for days 28 and 56, respectively. (
  • However, these approaches are limited by transplantation-related mortality ranging from 30% to 50% and disease relapse in a majority of patients. (
  • Manipulating this first wave of lymphocytes could be instrumental in reducing the 40% relapse rate following transplantation with reduced intensity conditioning. (
  • However, therapeutic targets for GVHD, tumor and infection are overlapping and these immunosuppressive therapies are associated with increased relapse, impaired immune reconstitution, and more infections. (
  • T cells are the key effectors of graft-versus-tumor immune responses, highlighted by the efficacy of donor lymphocyte infusions in mitigating disease relapse in certain conditions ( 6 ). (
  • We characterized the effect of transplanted donor mononuclear cells on relapse- and event-free survival after allogeneic bone marrow transplantation (BMT). (
  • Cox regression analyses evaluated risk strata, age, gender, and the numbers of nucleated cells, CD3-positive T cells, CD34-positive hematopoietic cells, and type 2 dendritic cells (DC2) as covariates for event-free survival, relapse, and nonrelapse mortality. (
  • Recipients of larger numbers of DC2 cells had significantly lower event-free survival, a lower incidence of chronic graft-vs-host disease, and an increased incidence of relapse. (
  • 10-15] Transplantation with fewer than 1 × 10 6 CD34-positive cells/kg from T-cell-depleted allogeneic bone marrow and peripheral blood stem cell grafts was associated with increased relapse and treatment-related mortality. (
  • 11,16] Recipients of T-cell-depleted bone marrow allografts have a decreased risk of developing graft-vs-host disease,[17,18] but experience delayed immune reconstitution and have an increased risk of infections, graft failure, and relapse. (
  • 1 However, infection, 2 graft-versus-host disease (GVHD), 3 and relapse 4 are still the most challenging sequelae to address to improve the outcomes of all patients after allogeneic transplantation. (
  • An analysis of 2254 patients receiving bone marrow transplants for acute myeloid leukemia (AML), acute lymphoblastic leukemia, and chronic myeloid leukemia showed lower rates of relapse in patients with non-T-cell-depleted allografts with GVHD, compared to those receiving T-cell-depleted allografts without GVHD. (
  • Future directions may include testing of vaccination strategies in the early post-transplantation setting for relapse prevention. (
  • Graft-versus-host-disease (GVHD) is a major cause of non-relapse mortality in patients receiving an allogenic hematopoietic cell transplantation (alloHCT), of which approximately 8,000 are performed in the US annually. (
  • In collaboration with Prof. Hans Stauss, we are also using genetic engineering to modify the behaviour of anti-tumour T cells in vivo to subvert tolerance mechanisms that lead to relapse of cancers after initial control. (
  • Peripheral blood cells will be obtained from patients with AML at first diagnosis or relapse, who are deemed eligible for AHSCT. (
  • We hypothesize that these autologous T cell infusions will be safe and effective at decreasing relapse rates following autologous stem cell transplantation. (
  • While T cell depletion reduces GVHD, its effect on immune reactivity may lead to an increased risk of relapse of certain leukemias after transplantation. (
  • The natural killer (NK) cells are central players in innate immunity particularly regarding the surveillance against malignant tumors ( 1 , 2 ). (
  • Thus, besides well-known IL-15 biologic functions in host immunity, this study shows that IL-15-based ALT-803 could activate CD8 + CD44 high memory T cells to acquire a unique innate-like phenotype and secrete IFN-γ for nonspecific tumor cell killing. (
  • They belong to innate immune cells but they have a link with adaptative immunity. (
  • Natural Killer (NK) cells are lymphocytes of innate immunity that respond to virus infected and tumor cells. (
  • NSG™ and NSG™-SGM3 mice are a proven host for engraftment of human tumors or establishment of human immunity following hematopoietic stem cell transplantation. (
  • T cells play a central role in immunity against infectious diseases and cancer. (
  • and finally ( c ) donor lymphocyte infusion (DLI) for posttransplant relapsed CLL effectively generates donor-derived tumor immunity against CLL ( 7 ). (
  • Innate immunity, encompassing monocytes, granulocytes, and NK cells, normally recovers in the first weeks to months after allo-HCT ( 3 , 4 ). (
  • A T cell , or T lymphocyte , is a type of lymphocyte (a subtype of white blood cell ) that plays a central role in cell-mediated immunity . (
  • Dendritic cells (DCs) 3 constitute a system of rare APCs that play crucial roles in the elicitation of T cell-dependent immunity ( 1 , 2 ). (
  • Although it is known that DCs are critical in initiating T cell immunity, emerging evidence suggests that DCs also play roles in the regulation of such responses. (
  • Effector cells of Innate and adaptive Immunity. (
  • Our scientists are world leaders in the study of innate and adaptive immunity, host-microbiota interactions, and mechanisms of immune regulation. (
  • Immunologist Michel Sadelain studies the mechanisms governing transgene expression, stem cell engineering, and genetic strategies to enhance immunity against cancer. (
  • The laboratory has recently demonstrated that IL33/ST2 pathway triggering in IL-9-secreting T cells decreases GVHD while maintaining tumor immunity through an enhanced GVL effect. (
  • Specifically Differentiated T Cell Subset Promotes Tumor Immunity over Fatal Immunity. (
  • Given the central role of DCs in adaptive immunity, results from these studies may have significant implications in the improvement of tumor immunity and control of other inflammatory disorders such as graft-rejection of transplanted organs and autoimmune diseases in broad context. (
  • Understanding of role of Delta-like ligand 4+ dendritic cells in alloimmunity and tumor immunity will lead to the development of novel and clinically relevant approaches to augment antitumor immunity, which could be potentially beneficial to approximately 10,000 new patients who receive allogeneic bone marrow transplantation every year. (
  • Enhanced immunity can also lead to immune-related adverse events due to on- or off-target effects. (
  • Thus, valid in vitro immune monitoring strategies should broaden the understanding of CMV immunity, GvL and GvHD, which seems essential for further improvements in allogeneic stem cell transplantation (SCT). (
  • These naïve and early memory CD8+ T cell populations are believed to play a key role in promoting immune reconstitution and viral immunity following cord blood transplantation. (
  • Enhancing the survival and immunological properties of T cells, and in particular those of naïve CD8+ T cells, may have significant therapeutic implications for harnessing immune memory in the context of both pathogen- and tumor-specific immunity. (
  • As Dr. Brenner explains, "This work was the forerunner of our later efforts to improve antiviral and antitumor immunity by adoptive transfer of T cells. (
  • Differentiating myeloid cells, bone remodeling by osteoblasts and osteoclasts, stimuli of the innate immunity as well as of the nervous system, including signals emanating the circadian clock, highly regulate various aspects of HSPC function, including egress, recruitment and mobilization. (
  • Immune Biology of Allogeneic Hematopoietic Stem Cell Transplantation: Models in Discovery and Translation, Second Edition once again provides clinical and scientific researchers with a deep understanding of the current research in this field and the implications for translational practice. (
  • Our primary aim was to analyze the impact of graft composition on immune reconstitution and clinical outcomes after transplantation. (
  • Early lymphocyte immune reconstitution is associated with improved clinical outcomes after transplantation ( 6 ). (
  • IFN-α has undergone extensive clinical evaluation during the past 2 decades in metastatic renal cell carcinoma. (
  • The regulation of T reg cells was suggested to be one mechanism of action of immunotherapy for cancer, and this has been examined in clinical trials [ 17 ]. (
  • They will present early clinical studies that demonstrate the safety of administration of ex vivo expanded NK cells after transplantation using feeder cells that express membrane-bound IL-21. (
  • Previous reports have suggested that immune-based treatments may be effective in sarcoma, but such approaches have not yet become part of standard clinical practice. (
  • Adoptive cell transfer (ACT) of T cells has great clinical potential, but the numerous variables of this therapy make choices difficult. (
  • In infectious diseases, many studies have shown that specific T-cell activation correlates with improved clinical outcome. (
  • nevertheless, adoptive cell transfer (ACT) therapy may be successful in selected patients with advanced metastatic melanoma, with about 50% to 70% of patients experiencing objective clinical responses after transfer of in vitro expanded T cells derived from autologous tumor-infiltrating lymphocytes (TIL). (
  • ACT may also show clinical benefit in patients with synovial cell sarcomas and some leukemias ( 3 ). (
  • For about 10 years, researchers have run clinical trials of ACT with genetically engineered (TCR-transfected) T cells for patients with cancer, many of whom have experienced clinical responses ( 4 ). (
  • Going beyond the current use of monoclonal antibodies (mAb) targeting immune checkpoints in clinical practice, we will offer an overview of new combinatory therapeutic perspectives where cHL immunotherapy may be considered. (
  • In recent years, natural killer (NK) cell strategies for cancer immunotherapy have stimulated increasing interest but their clinical application has largely been restricted to the haploidentical hematopoietic stem cell transplantation setting, where natural killer immunoglobulin receptor mismatches between the donor and recipient are exploited to enhance the graft-antileukemia effect. (
  • Accordingly, the first clinical trials using adoptive transfer of autologous NK cells have failed to produce significant therapeutic effects ( 2 , 3 ). (
  • Computational Oncology studies that integrate clinical, genomic, and imaging data to explore the dynamics of tumor heterogeneity and. (
  • I am a physician scientist at Stanford University/Lucile Packard Children?s Hospital, with a clinical and research focus in stem cell transplantation. (
  • T cells and natural killer cells are both thought to be important in the graft- versus -leukemia effect, and both cell types are amenable to ex vivo manipulation and clinical manufacture, making them versatile immunotherapeutics. (
  • 9 From a therapeutic perspective, both cell types are amenable to ex vivo manipulation and clinical manufacture, thus making them versatile immunotherapeutics. (
  • The transfer of HAdV-specific donor T cells in patients with HAdV viremia has been evaluated in several clinical phase I/II trials and preliminary data suggest that this approach may be feasible and effective. (
  • The lab's work in allogeneic hematopoietic cell transplantation, GVHD and GVL biology and novel treatment involves implementing non-invasive blood tests for risk stratification of complications following allogeneic hematopoietic cell transplantation and validating the biological and clinical significance of those biomarkers. (
  • This represents a new treatment option for patients with advanced renal cell carcinoma, who will now have access to KEYTRUDA as part of a first-line combination regimen," said Dr. Scot Ebbinghaus, vice president, clinical research, Merck Research Laboratories. (
  • PresseBox) ( Martinsried/Munich , 01.04.16 ) Medigene AG (MDG1, Frankfurt, Prime Standard), a clinical stage immune-oncology company, announced the treatment start of the first phase II-patient in its dendritic cell (DC) vaccine clinical phase I/II trial in acute myeloid leukaemia (AML). (
  • Secondary objectives of the study are induction of tumour-specific immune response, control of minimal residual disease (MRD), and clinical response/time to progression (TTP). (
  • CD40L has a well-established role in enhancing the immunostimulatory capacity of normal and malignant B cells, but a formulation suitable for clinical use has not been widely available. (
  • I have studies the mechanism of monoclonal antibody therapy in lymphoma patients and am currently working on designing new strategy to enhance the clinical efficacy of antibody therapy by infusing expanded NK cells. (
  • KEYTRUDA is already an established treatment option for non-small cell lung cancer, and today's approval in small cell lung cancer demonstrates our commitment to bringing forward new treatment options for patients with advanced, difficult-to-treat cancers," said Dr. Jonathan Cheng, vice president, oncology clinical research, Merck Research Laboratories. (
  • We look forward to continuing to advance important clinical research in small cell lung cancer. (
  • Small cell lung cancer, which accounts for 10 to 15% of all lung cancers, is often diagnosed at an advanced stage where the prognosis is very poor and there have historically been limited treatment options," said Dr. Patrick Ott, MD, PhD, clinical director, Center for Immuno-Oncology, Dana-Farber Cancer Institute. (
  • The approval of KEYTRUDA in small cell lung cancer provides an additional treatment option for patients based on the clinical response rates from KEYNOTE-158 and KEYNOTE-028. (
  • These novel scientific and clinical observations raise the possibility that T cell-related mechanisms may also be enhanced using ex vivo pharmacologic modulation strategies. (
  • The following will provide you with details of current clinical applications of graft engineering by stem cell enrichment. (
  • uly 24, 2014 -Malcolm K. Brenner, MD, PhD, Baylor College of Medicine (Houston, TX) has devoted his career in basic and clinical research toward understanding how tumors are able to escape detection by the body's immune defense system, and developing genetically modified T cells that can effectively target tumors. (
  • The Award Selection Committee selected scientists that had devoted much of their careers to cell and gene therapy research and had made a seminal contribution to the field--defined as a basic science or clinical advance that greatly influenced progress in translational research. (
  • Its sister journals, Human Gene Therapy Methods , published bimonthly, focuses on the application of gene therapy to product testing and development, and Human Gene Therapy Clinical Development , published quarterly, features data relevant to the regulatory review and commercial development of cell and gene therapy products. (
  • Wiskott Aldrich syndrome) and metabolic disorders (e.g. type 1 diabetes ), infantile brain damage (e.g. cerebral palsy), oncological (e.g. multiple myelomas, neuroblastoma) and hematological diseases (e.g. hematopoietic disorders, beta thalassemia) as well as in the scope of a clinical study on type 1 diabetes. (
  • Currently, scientists are more than anxious to examine new clinical fields to apply stem cells. (
  • This proposal involves a novel multi-center clinical trial testing the safety and efficacy of infusing autologous cytotoxic T cells in patients with acute myeloid leukemia who have recently undergone autologous stem cell transplantation. (
  • The major source for clinical transplantation protocols is via peripheral blood (PB) mobilization of BM derived HSPCs. (
  • The Clinical and Economic Impact of Cytomegalovirus Infection in Recipients of Hematopoietic Stem Cell Transplantation. (
  • Stem cell transplants fall into two categories: autologous and allogeneic. (
  • A variety of studies support the role of larger numbers of CD34-positive cells in the graft in faster hematopoietic reconstitution after autologous and allogeneic transplantation. (
  • Autologous and allogeneic haematopoietic stem cell (HSC) transplantation has been performed in patients with various malignant and non-malignant haematological disorders for more than 50 years. (
  • Their ability to kill tumor cells makes them promising to evaluate as effector cells for immunotherapy. (
  • I believe this review series will deepen our understanding of transplantation immunology and recent progress in new immunotherapy-based therapy. (
  • Here we review prior trials of immunotherapy including nonspecific immunomodulators, vaccines, and adoptive T-cell therapy. (
  • Novel natural killer (NK) cell-directed strategies in cancer immunotherapy aim at specifically modulating the balance between NK cell receptor signals toward tumor-specific activation. (
  • First successfully performed in 1959, allogeneic hematopoietic stem cell transplantation (allo-HCT) encompassed the earliest forms of stem cell therapy, cancer immunotherapy, and individualized treatment ( 1 ). (
  • These efforts laid the foundation for the recent exciting era of cancer immunotherapy, which includes immune checkpoint blockade, personal neoantigen vaccines, and adoptive T cell transfer. (
  • By better understanding of how populations of NK cells and T cells are built up by individual cells with varying capacity to respond to stimuli we will be able to improve current methods for immunotherapy. (
  • A feature that makes a TAA ideal for immunotherapy is the dependency of the malignant cells on the expression of the TAA. (
  • CAR-T cell therapy is a form of immunotherapy, widely recognized as a new and highly promising frontier in cancer therapy. (
  • Scientists from our program have played a central role in the development of several types of immunotherapy that are currently transforming cancer care, including checkpoint blockade and CAR T cell therapy. (
  • Cancer Immunologist Andrea Schietinger investigates immune responses to cancer, molecular mechanisms underlying tumor-induced T cell dysfunction, and new approaches for cancer immunotherapy. (
  • The primary objective is to prove feasibility and safety of active immunotherapy with Medigene's dendritic cells. (
  • T cell exhaustion and a suppressive bone marrow microenvironment have been implicated in disease progression, and once these are established, immunotherapy appears largely ineffective. (
  • Graft-versus-host-disease, Graft-versus-leukaemia, T cell immunotherapy. (
  • 9. Abramson JS, Palomba L, Gordon L. Transcend NHL 001: immunotherapy with the CD19-Directd CAR T-cell product JCAR017 results in high complete response rates in relapsed or refractory B-cell non-Hodgkin lymphoma. (
  • Bispecific T-cell engagers for cancer immunotherapy. (
  • This innovative protocol will determine whether cellular immunotherapy with autologous cytotoxic T cells is safe and has the potential for therapeutic benefit in patients with AML. (
  • Bone marrow transplantation was pioneered at the Fred Hutchinson Cancer Research Center from the 1950s through the 1970s by E. Donnall Thomas , whose work was later recognized with a Nobel Prize in Physiology and Medicine. (
  • Dr. Thomas' work showed that bone marrow cells infused intravenously could repopulate the bone marrow and produce new blood cells . (
  • Other patients who receive bone marrow transplants include pediatric cases where the patient has an inborn defect such as severe combined immunodeficiency or congenital neutropenia and was born with defective stem cells. (
  • Other conditions that bone marrow transplants are considered for include thalassemia major , sickle-cell disease , myelodysplastic syndrome , lymphoma , Hodgkin's disease , and multiple myeloma . (
  • A major limitation of allogeneic bone marrow transplantation is a shortage of donors. (
  • The science of bone marrow transplantation arose from the realization that irradiation causes lethal bone marrow failure ( 1 ), thus generating the idea that intensifying irradiation or use of cytotoxic drugs at myeloablative doses could cure bone marrow diseases. (
  • Bone marrow, the spongy tissue inside our bones, is the factory for blood cells. (
  • In this study, we show that a single dose of ALT-803, but not IL-15 alone, eliminated well-established 5T33P and MOPC-315P myeloma cells in the bone marrow of tumor-bearing mice. (
  • The term haematopoietic stem cell (HSC) refers to cells made in the blood factory or bone marrow that have the potential to grow into almost any type of blood cell. (
  • The treatment that immediately precedes infusion of HSC is called conditioning therapy and is given to help kill tumour cells, "wipe out the memory" of the recipient's immune system, and create "space" within the bone marrow for the incoming stem cells to grow. (
  • The reinfusion of the patient's own stem cells acts to rescue the bone marrow from toxicity. (
  • Sykes M. Immune tolerance in recipients of combined haploidentical bone marrow and kidney transplantation. (
  • In conclusion, content of donor DC2 cells was associated with decreased chronic graft-vs-host disease and graft-vs-leukemia effects consistent with Th2/Tc2 polarization of donor T cells following allogeneic bone marrow transplantation. (
  • The optimal numbers for each cell type in the bone marrow or peripheral blood progenitor cell allograft are not known. (
  • Physician-scientist Marcel R. M. van den Brink studies the immunology of bone marrow transplantation with a particular focus on intestinal microbiome and strategies to enhance thymus and immune reconstitution. (
  • Methods for increasing hematopoietic cells, including platelets and erythrocytes, in patients receiving bone marrow or peripheral blood stem cell transplants are disclosed. (
  • administering the collected bone marrow cells or peripheral blood stem cells to a recipient patient, whereby platelets or erythrocytes in the recipient patient are increased. (
  • 5. A method according to claim 1 wherein the cells are bone marrow cells. (
  • 7. A method according to claim 1 further comprising administering to the recipient patient, after or concurrently with administering the bone marrow cells or peripheral blood stem cells, an amount of thrombopoietin sufficient to enhance platelet recovery or erythrocyte recovery. (
  • More specifically, the first MiHA was discovered when bone marrow transplantation occurred between opposite sexes. (
  • The female recipient obtained MHC-matched bone marrow cells but still had active cytotoxic T cells (CD8+). (
  • The CD8+ T cells were active and targeted the male bone marrow cells. (
  • The male bone marrow cells were found to be presenting a peptide in the MHC groove encoded by a gene on Y chromosome. (
  • The work on proteomics and discovery of biomarkers includes the use of an omics workflow system as a discovery engine for new biomarkers of complications of post-allogeneic bone marrow transplantation, including acute and chronic graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) as well as antitumoral signatures following antibody-based or cell-based immunotherapies. (
  • The stem cells are collected from donor's blood through a process known as apheresis after a certain period of daily subcutaneous injections of Granulocyte-colony stimulating factor, serving to mobilize stem cells from the donor's bone marrow into the peripheral circulation. (
  • These immune cells originate as precursor cells , derived from bone marrow , [1] and develop into several distinct types of T cells once they have migrated in to the thymus gland - for which these cells are named. (
  • All T cells originate from c-kit + Sca1 + haematopoietic stem cells (HSC) which reside in the bone marrow. (
  • Thus, Dll4 activation of Notch signaling is important for GVH responses;3) Flt3L and Toll-like receptor signaling were essential for induction of Dll4+DCs from cultured bone marrow cells. (
  • Bone marrow transplantation was the original term used to describe the collection and transplantation of hematopoietic stem cells, but with the demonstration that the peripheral blood and umbilical cord blood are also useful sources of stem cells, hematopoietic cell transplantation has become the preferred generic term for this process. (
  • Homing is also influenced by the interaction of cell-surface molecules, termed selectins , on bone marrow endothelial cells with ligands, termed integrins , on early hematopoietic cells. (
  • Human hematopoietic stem cells can survive freezing and thawing with little, if any, damage, making it possible to remove and store a portion of the patient's own bone marrow for later reinfusion following treatment of the patient with high-dose myelotoxic therapy. (
  • Multiple myeloma (MM), a bone marrow-resident hematological malignancy of plasma cells, has remained largely incurable despite dramatic improvements in patient outcomes in the era of myeloma-targeted and immunomodulatory agents. (
  • 1] cel s, but since the treatment targets all rapidly dividing cel s in the Following transplantation of autologous gene-modified HSCs body, it also depletes the HSC compartment in the bone marrow. (
  • A similar immune reaction can occur in the lymphoid organs and bone marrow, a process co-opted therapeutically to achieve a graft-versus-leukaemia (GVL) effect. (
  • Be The Match® is a global leader in bone marrow transplantation. (
  • As early as in 1957, allogeneic bone marrow was transplanted in radiation victims for the first time. (
  • Furthermore, the focus regarding the application of autologous stem cells - especially from the umbilical cord - will be increasingly in the field of regenerative medicine (i.e. the regeneration of bone, cartilage, muscle, and nerve tissue or the treatment of autoimmune diseases) in the future. (
  • Hematopoietic stem and progenitor cells (HSPCs) continuously egress out of the bone marrow (BM) to the circulation under homeostatic conditions. (
  • Enrichment of stem cells in peripheral blood can be achieved by inducing mobilization of stem cells from the BONE MARROW. (
  • It then moves on to discuss the immunobiology mechanisms that influence graft-versus-host disease (GVHD), graft-versus-leukemia effect, and transplantation success. (
  • As one example, large numbers of patients with leukemia have benefited from the graft-versus-leukemia effect induced and maintained by donor T cells after allogeneic hematopoietic stem cell transplantation. (
  • Calcineurin inhibitors, T-cell depletion strategies, and immunomodulators have helped to prevent graft- versus -host disease, but have a negative impact on the graft- versus -leukemia effect. (
  • We discuss the contributions of each cell type to graft- versus -leukemia effects, as well as the current research directions in the field as related to adoptive cell therapy after hematopoietic stem cell transplantation. (
  • In this pilot trial, we assessed safety and feasibility of a WT1 peptide-loaded donor-derived dendritic cell (DC) vaccine given with DLI designed to enhance and direct the graft-versus-leukemia effect. (
  • The reconstituted cells can be pathogen-specific (e.g. cytomegalovirus (CMV)-reactive T cells), leukemia-specific (i.e. graft versus leukemia (GvL) effect) or recipient-specific (e.g. (
  • A major goal in limiting complications after alloHSCT therefore involves targeting key proinflammatory mediators, like IL6, IL23, and IFNγ, that can promote GvHD ( 1 ) without broadly impairing the immune response that mediates the desired graft-versus-leukemia or graft-versus-tumor (GvL/GvT) effect. (
  • Certain immune cells, called T cells, contained in the donor HCT graft can cause a "graft versus leukemia" (GVL) effect which eliminates leukemic cells. (
  • NK cells are the most efficient effector cells of the innate immune system and have the capability to eliminate leukemic cells. (
  • Effector cells are the superset of all the various T cell types that actively respond immediately to a stimulus, such as co-stimulation . (
  • Determine the effects of this regimen on the functional and molecular status of effector cells (i.e. (
  • Residual, refractory or relapsed cancer is treated by immunostimulation in the presence of allogeneic immune effector cells, optimally in combination with radiation therapy. (
  • The discovery that the infusion of allogeneic hematopoietic stem cells can "rescue" patients from lethal marrow toxicity and give rise to a new donor-derived immunohematopoietic system resulted in successful treatments for patients with malignant or nonmalignant hematologic disease ( 2 , 3 ). (
  • Multiple myeloma is a plasma cell malignancy, accounting for more than 1% of neoplastic diseases and 14% of all hematologic cancers ( 1 ). (
  • But some scholars reported the ATG delayed immune reconstitution and hematologic reconstitution and leaded to the increase of the incidence of virus and fungal infections after transplantation. (
  • AbbVie is leveraging its areas of strength to investigate therapies that are designed to target markers on cancer cells. (
  • Multiple myeloma tumor cells are susceptible to immune cell recognition and elimination, as shown by the potentially curative graft-versus-myeloma activity observed in some patients following allogeneic hematopoietic stem cell transplantation and donor lymphocyte infusion therapies ( 2 ). (
  • In the autologous setting, additional dose intensification of treatment may be possible with targeted therapies like radiolabeled antibodies that deliver higher doses to the tumor. (
  • NSG™ and NSG™-SGM3 Mice engrafted with human hematopoetic stem cells represent powerful tools for studying oncology, infectious disease, and hematopoiesis and are helping accelerate the development of novel therapies. (
  • My long-term career goal is to develop a research program focusing on immune tolerance in stem cell transplantation and become a leader in the development of improved therapies for preventing or treating graft-versus-host disease. (
  • This research is also focused on discovering inhibitors of drug targetable biomarkers and new cell therapies to alleviate GVHD and increase GVL. (
  • Haematopoietic stem cells (HSCs) support blood system homeostasis and are also used clinically in cell and gene therapies. (
  • We are interested in studying the biology of this important stem cell population and developing new HSC-based therapies. (
  • These catastrophic events are not only linked to tumour initiation, they also play a central role in cancers ability to evolve and acquire new aggressive traits, such as the ability to metastasize, or become resistant to anti-cancer therapies. (
  • Dr. Childs has recently focused efforts on developing methods to improve the outcome of allogeneic stem cell transplantation for aplastic anemia where immunosuppressant therapies have failed and to improve the outcome for patients who lack a matched donor. (
  • Therapies that optimize immune function therefore have the potential to improve the outcome of lymphoma patients. (
  • Major advances have been made over the last three decades with respect to gene modification of HSCs and transplantation strategies, ultimately culminating in the approval of two such therapies in Europe (Strimvelis for a rare primary immune deficiency, and LentiGlobin for beta-thalassaemia). (
  • So far, stem cell deposits stored at Vita 34 and prepared in high quality for medical therapies have been applied in 30 patients. (
  • Therapies that use cancer-recognizing immune T cells are especially promising. (
  • Once activated, NK lymphocytes kill tumor cells via FcgRIIIA (CD16) which can trigger antibody-dependent cellular cytotoxicity (ADCC) on encountering target cells opsonized with IgG, via the Fas/Fas-L pathway and via cytotoxic granules (perforin/granzyme) secretion ( 1 , 8 ). (
  • Additional evidence for the role of donor cells in GVT effects came from findings that recurrent leukemia could be successfully treated solely by infusing additional allogeneic lymphocytes ( 6 ). (
  • T lymphocytes from the adaptive immune system are essential actors in the allo-recognition involved in both GVT effects and GVHD ( 8 - 10 ). (
  • NK cells are lymphocytes who play a role in the control of viral infections , tumor and fœtal tolerance. (
  • After allogeneic transplantation, NK cells are the first reconstituting lymphocytes, but are dysfunctional. (
  • A new step in this direction was taken in a study published in this issue of Cancer Discovery by Ma and colleagues ( 5 ), who analyzed T cells from 3 representative patients selected from a trial of 14 patients with melanoma who underwent ACT therapy with lymphocytes transfected with the high-affinity Melan-A/MART-1-specific TCR "F5" ( 4 ). (
  • T cells can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T-cell receptor on the cell surface . (
  • Natural killer (NK) cells of the innate immune system are cytotoxic lymphocytes that play an important roles following transplantation of solid organs and hematopoietic stem cells. (
  • T lymphocytes, and platelets, as well as cells comprising the fixed macrophage population, including Kupffer cells of the liver, pulmonary alveolar macrophages, osteoclasts, Langerhans cells of the skin, and brain microglial cells. (
  • However, in contrast to the 100% donor hematopoietic engraftment typical of myeloablative transplantation, such nonmyeloablative transplants typically resulted in a state of mixed hematopoietic chimerism. (
  • recipients of fewer CD34-positive cells had delayed hematopoietic engraftment and increased death from infections. (
  • Upon adoptive transfer in a murine mixed hematopoietic chimerism model, orthogonal IL-2 injection significantly promoted orthogonal IL-2R+Foxp3GFP+CD4+ cell proliferation without increasing other T cell subsets and facilitated donor hematopoietic cell engraftment followed by acceptance of heart allografts. (
  • The TCR alpha/beta/CD19-depleted HPCs are used for allogeneic hematopoietic cell transplantation (HCT) and may allow for rapid and sustained engraftment, rapid immune reconstitution, and may prevent or reduce graft-versus-host disease (GvHD). (
  • In addition to the well-established effect of dmPGE2 on enhancing the engraftment properties of hematopoietic stem cells, our molecular characterization and immunological assessments provide new evidence that dmPGE2 can also significantly improve the functional properties of T cells contained within human umbilical cord blood," stated Dr. Vicki Boussiotis, M.D., Ph.D., Professor, Department of Medicine, Harvard Medical School, and senior author on the Blood Cancer Journal publication. (
  • In preclinical testing, PROHEMA ® has demonstrated the potential to accelerate engraftment and to drive durable hematopoietic reconstitution, without the need for multi-week expansion protocols. (
  • Rescue haploidentical peripheral blood stem cell transplantation for engraftment failure: a single-centre case series. (
  • Immunology Program Chair Alexander Rudensky focuses on immunological tolerance and the differentiation and function of T cells. (
  • Dr. Brenner received a PhD in immunology and early in his career sought to understand how B cells interact with T cells to produce antibodies. (
  • Aggressive T-cell lymphomas (ATCLs), including peripheral T-cell lymphoma and T lymphoblastoid cell lymphoma/leukemia, represent 10% to 15% of non-Hodgkin's lymphomas (NHLs) in adults(1). (
  • ATG also has pro-apoptotic activity against the majority of primary leukemia cells, particularly those cells from lymphatic origin. (
  • We investigated whether 2B4-enhanced activation signals can redirect the cytolytic function of human NK cells to NK cell-resistant and autologous leukemia and tumor targets. (
  • In vitro -stimulated NK cells from healthy donors and pediatric leukemia patients were gene modified with CD19 or G D2 -specific chimeric receptors containing either the T-cell receptor ζ or 2B4 endodomain alone or combined. (
  • For these reasons, NK cell-based immunotherapies have mostly focused on the haploidentical hematopoietic stem cell transplantation setting, where KIR:MHC class I mismatches between the donor and recipient were found by many investigators to contribute to the control of residual myeloid leukemia cells ( 4 , 5 ). (
  • PURPOSE: This phase II trial is studying how well giving bryostatin 1 together with rituximab works in treating patients with B-cell non-Hodgkin's lymphoma or chronic lymphocytic leukemia that has not responded to previous treatment with rituximab. (
  • Determine the feasibility and safety of bryostatin 1 and rituximab in patients with rituximab-refractory indolent B-cell non-Hodgkin's lymphoma or chronic lymphocytic leukemia (CLL). (
  • 5 Over the last several decades, the introduction of calcineurin inhibitors, T-cell depletion strategies, and immunomodulators has helped to prevent GVHD, but at a cost - with inhibition of the donor-specific immune response including the graft-versus-tumor/leukemia (GVL) effect. (
  • CML66-derived peptide-specific CTL efficiently lysed human leukemia cells, but not normal cells, in a HLA-A*2402-restricted fashion. (
  • Quantitative real-time polymerase chain reaction revealed that CML66 mRNA is expressed abundantly in primary acute myeloid leukemia cells, acute lymphoid leukemia cells, and chronic myelogenous leukemia cells in advanced phase, and that the expression level of CML66 mRNA in normal cells is low compared with that in leukemia cells. (
  • Chronic lymphocytic leukemia (CLL), a disease of clonal CD19+ CD5+ CD23+ B cells, is sensitive to immune modulation. (
  • Large numbers (109-1010) of CD8+ T cells that are myeloid leukemia-specific are generated in this manner. (
  • Although Tregs play an important role for the maintenance of peripheral tolerance and suppression of GVHD, Tregs do not inhibit cytotoxic T lymphocyte function against tumor and have little impact on GVL effects. (
  • Understanding the interactions between human immune cells and tumors is paramount when devising treatment strategies that prevent tumor evasion of immune cells and improve cytotoxic responses. (
  • ATG is used in allogeneic SCT for the prophylaxis of graft versus host disease by in vivo T cell depletion, including the complement-dependent cytotoxic response, antibody-dependent cell-mediated cytotoxicity, the opsonophagocytic role of phagocytic cells and induced apoptosis(3). (
  • 2013) Classification of human natural killer cells based on migration behavior and cytotoxic response. (
  • T helper cells (T H cells) assist other white blood cells in immunologic processes, including maturation of B cells into plasma cells and memory B cells , and activation of cytotoxic T cells and macrophages . (
  • CD8+ T cells, also known as "Killer cells", are cytotoxic - this means that they are able to directly kill virus-infected cells as well as cancer cells. (
  • The selective outgrowth of normal progenitor cells over neoplastic cells to achieve tumor-free autografts may ameliorate the results of autologous transplantation. (
  • M-CSF improves protection against bacterial and fungal infections after hematopoietic stem/progenitor cell transplantation. (
  • The process of differentiation then proceeds to a common lymphoid progenitor (CLP), which can only differentiate into T, B or NK cells. (
  • A preparation of hematopoietic progenitor cells (HPCs) from a haploidentical donor that have been depleted of T-cell receptor (TCR) alpha and beta (TCRa/b+) as well as CD19-positive (CD19+) cells, that can potentially be used for immune reconstitution purposes. (
  • ALT-803, a complex of an interleukin (IL)-15 superagonist mutant and a dimeric IL-15 receptor αSu/Fc fusion protein, was found to exhibit significantly stronger in vivo biologic activity on NK and T cells than IL-15. (
  • ALT-803 treatment stimulated CD8 + T cells to secrete large amounts of IFN-γ and promoted rapid expansion of CD8 + CD44 high memory T cells in vivo . (
  • Adeegbe D, Serafini P, Bronte V, Zoso A, Ricordi C, Inverardi L. In vivo induction of myeloid suppressor cells and CD4(+)Foxp3(+) T regulatory cells prolongs skin allograft survival in mice. (
  • PDX models provide researchers with the ability to work with tumors directly from patients within a living (in vivo) system, making them a. (
  • However, it is technically challenging to expand Tregs ex vivo for the purpose of infusing large numbers of cells in the clinic. (
  • We demonstrate an innovative approach to engineering an orthogonal IL-2/IL-2 receptor (IL-2R) pair, the parts of which selectively interact with each other, transmitting native IL-2 signals, but do not interact with the natural IL-2 or IL-2R counterparts, thereby enabling selective stimulation of target cells in vivo. (
  • Recent evidence suggests that distinct DC subsets direct different classes of immune responses in vitro and in vivo. (
  • The differential mobilization of distinct DC subsets or DC precursors by in vivo administration of FL and G-CSF offers a novel strategy to manipulate immune responses in humans. (
  • Compared to other cells, both T cells and NK cells are amenable to ex vivo manipulation, making them excellent sources of biological therapeutics. (
  • In NSG mice transplanted with human skin xenografts, B-I09 protects human skin grafts from alloreactive T cell rejection in vivo. (
  • To test the efficacy of B-I09 in vivo, NSG mice were transplanted with a human skin graft (1 cm 2 ) and later injected with 5x106 human peripheral blood mononuclear cells (PBMC) allogeneic to the skin. (
  • The main risk factor for HAdV infection is prolonged immunosuppression, attributable either to in vivo or ex vivo T-cell depletion, prolonged lymphopenia, or to GvHD-associated immunosuppressive posttransplant therapy. (
  • PROHEMA ® is produced through a proprietary, two-hour, ex vivo cell modulation process that results in rapid activation of key biological pathways involved in homing, proliferation and survival of HSCs. (
  • Ex vivo gene modification of HSCs for autologous transplantation opens up new therapeutic avenues for genetic and infectious diseases. (
  • The down-regulation of HLA class I molecules is an immune escape mechanism frequently used by tumor cells ( 6 ) that, accordingly, should not be recognized by the T-lymphocyte receptor (TCR). (
  • The absence of normal HLA class I molecule on tumor cells should lead to NK-cells activation, more efficiently when co-stimulatory molecules and ligands for NK activating receptor are present at tumor cell surface. (
  • Binding of PD-L1 and PD-L2 to the programmed cell death protein 1 (PD-1) receptor found on T cells inhibits T-cell proliferation and cytokine production. (
  • Pembrolizumab is an anti-PD-1 monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, thereby releasing PD-1 pathway-mediated inhibition of the immune response, including antitumor immune response. (
  • Cytomegalovirus (CMV) infection stimulates and expands a distinctive NK cell population that expresses the NKG2C receptor and exhibits enhanced effector functions. (
  • The signaling lymphocyte activation molecule-related receptor 2B4 (CD244) is an important regulator of NK cell activation. (
  • These data indicate that the 2B4 receptor has a potent costimulatory effect in NK cells. (
  • The majority of human T cells, termed alpha beta T cells (αβ T cells), rearrange their alpha and beta chains on the cell receptor and are part of the adaptive immune system . (
  • Central memory T cells (T CM cells) express CD45RO, C-C chemokine receptor type 7 (CCR7), and L-selectin (CD62L). (
  • Selective expansion of regulatory T cells using an orthogonal IL-2/IL-2 receptor system facilitates transplantation tolerance. (
  • Our data indicate that selective target cell stimulation enabled by the engineered orthogonal cytokine receptor improves Treg potential for the induction of organ transplantation tolerance. (
  • NK cells expressing an inhibitory KIR-binding self-HLA can be activated when confronted with allografts lacking a ligand for the inhibitory receptor. (
  • Following the response of the adaptive immune system, NK cells can further destroy allograft endothelium by antibody-dependent cell-mediated cytotoxicity (ADCC), triggered through cross-linking of the CD16 Fc receptor by donor-specific antibodies bound to allograft. (
  • This review summarizes the role of NK cells in allograft rejection and proposes mechanistic concepts that indicate a prominent role for KIR-HLA interactions in facilitating NK cells for Fc receptor-mediated ADCC effector function involved in antibody-mediated rejection of solid organ transplants. (
  • This cytokine receptor binds to B-lymphocyte chemoattractant (BLC), and is involved in B-cell migration into B-cell follicles of spleen and Peyer patches. (
  • Neoplastic Cells of Primary Cutaneous CD4+ Small/Medium-sized Pleomorphic T-cell Lymphoma Lack the Expression of Follicular T-helper Cell Defining Chemokine Receptor CXCR5. (
  • The earliest cells which arrived in the thymus are termed double-negative, as they express neither the CD4 nor CD8 co-receptor. (
  • After the TCRα locus has been re-arranged, the cell will express the full TCR on the surface and upregulate the co-receptor genes CD4 and CD8 and be termed "double-positive" (DP) cells. (
  • The cells then downregulate the non-selected co-receptor and become single-positive either CD4+ or CD8+ T cells (SP cells). (
  • This induces pro-phagocytic signaling mediated by the binding of the pro-phagocytic signaling protein calreticulin (CRT), which is specifically expressed on the surface of tumor cells, to low-density lipoprotein (LDL) receptor-related protein (LRP), expressed on macrophages. (
  • T Cell Receptor mimic (TCRm) antibodies to low-density peptide epitopes from undruggable intracellular proteins presented in the context of major histocompatibility (MHC) molecules are therapeutically effective in mouse models of human cancers. (
  • B-cell receptor sequencing showed a B-cell repertoire with little evidence of somatic hypermutation in most patients. (
  • We developed general methods for crystallizing glycoproteins and determined the structures of key T-cell surface proteins including the first adhesion protein (CD2) and its ligand CD58, the costimulatory receptor CD28 and its ligand CD80, and the large tyrosine phosphatase CD45. (
  • The ability of the hematopoietic stem cell to home to the marrow following intravenous injection is mediated, in part, by an interaction between stromal cell-derived factor 1 (SDF1) produced by marrow stromal cells and the alpha-chemokine receptor CXCR4 found on stem cells. (
  • New immunotherapies based on checkpoint inhibition targeting the immune receptor TIGIT and the deletion of suppressive myeloid populations appear attractive, particularly after ASCT. (
  • Allogeneic transplants are also performed using umbilical cord blood as the source of stem cells. (
  • To understand the different types of stem cell transplants and how they work, we spoke with Borje S. Andersson, M.D., Ph.D. Here's what he had to say. (
  • What are the types of stem cell transplants? (
  • In the case of transplants using HSC derived from other people, the conditioning therapy also helps reduce the risk of the recipient's body killing or rejecting the incoming donor stem cells (graft rejection). (
  • Another type of HSC source is cord blood cells that are used in umbilical cord blood transplants. (
  • Cotransplantation with myeloid-derived suppressor cells protects cell transplants: A crucial role of inducible nitric oxide synthase. (
  • oday about 35,000 allogeneic Hematopoietic Stem Cell transplants are carried out annually worldwide and they are increasing each year. (
  • At present, the possible prophylactic effect of cord blood transplants is discussed and in a large-scale study examines, whether the transplantation of autologous cord blood prevents the outbreak of type 1 diabetes in high-risk children. (
  • Graft failure affects approximately 5% of allogeneic stem cell transplants, with a poor prognosis. (
  • T cell and natural killer (NK) cells have remarkable abilities to mediate targeted attack against virus-infected or malignant cells. (
  • The abnormal expression of TAA by malignant cells, either through overexpression or aberrant localization, can lead to preferential presentation of TAA-derived immunogenic epitopes on the target cell surface. (
  • The triggering event of NK-cells activation and killing of target cells results from a balance between activating and inhibitory signals sent by membrane receptors that either enhance or block the NK-mediated cytotoxicity ( 4 ). (
  • Inhibitory signals arise from interaction between HLA-specific inhibitory receptors, as the killer immunoglobulin-like receptors (KIR), NK group protein 2A (NKG2A), or Immunoglobulin-like transcript 2 (ILT-2) with HLA class I molecules, whereas the absence or abnormal expression of the later molecules induces NK-cells cytotoxicity ( 5 ). (
  • NK cells recognize self from non-self through a series of inhibitory and activating receptors engaged by the major histocompatibility complex (MHC) class 1 specific killer Ig-like receptors (KIRs) ( 19 ). (
  • Phenotypical study of NK cells: activating and inhibitory receptors, activation and differentiation's markers. (
  • NK cells express numerous activating and inhibitory receptors. (
  • Their activity is determined by the balance of signals from inhibitory and activating NK cell receptors. (
  • Indeed, engagement of activating NK cell receptors by ligands expressed on tumor cells can overcome inhibitory signals and stimulate NK cell responses even in the presence of autologous MHC class I ( 6 , 7 ). (
  • This mechanism is efficiently counteracted in many human tumors, where cells evade NK cell-mediated killing by shedding or intracellular retention of ligands for activating receptors ( 8 ). (
  • By rearranging gene segments during T-cell development, a large number of T cells with different T-cell receptors (TCR) are made that can potentially recognize an unlimited number of peptides in the context of MHC molecules. (
  • The Impact of HLA Class I-Specific Killer Cell Immunoglobulin-Like Receptors on Antibody-Dependent Natural Killer Cell-Mediated Cytotoxicity and Organ Allograft Rejection. (
  • The cumulative activating and inhibitory signals generated by ligation of the receptors regulates mature NK cell killing of target cells and their production of cytokines and chemokines. (
  • Chemokine and chemokine receptors could have played an important role in tumor angiogenesis and distant metastasis. (
  • RESULTS of gene-chips indicated that there was low or no expression of CCR10, CXCR1, CXCR3 and CXCR5 in BPH-1 cells, whereas the expression of these receptors in BPH-1 cells was increased by PBMCs, and the expression was high in LNCaP cells. (
  • Although B cell receptors can also recognize MHCs, immune responses seem to only be elicited by T cells. (
  • NK cells, at the frontier of innate and adaptive immune system, have a central role in tumor-cells surveillance as demonstrated in the setting of allogenic stem cell transplantation. (
  • Nevertheless, tumors develop various mechanisms to escape from NK innate immune pressure. (
  • T cells (right) and NK cells (left) are among the principal cellular effectors of the adaptive and innate immune responses, respectively. (
  • Noncytolytic control of viral infections by the innate and adaptive immune response. (
  • In this Review, we discuss immunologic approaches that directly target the malignant cell as well as approaches to optimize both the innate and adaptive immune response to the tumor. (
  • This delay in lymphoid reconstitution is exacerbated with age and results in severely dampened adaptive immune responses. (
  • And also Tregs are able to migrate into inflamed tissue and regulate the latter stage of immune responses. (
  • A new study takes advantage of a novel technology for characterizing the T-cell responses of patients. (
  • Three patients had initial transient tumor responses followed by disease progression within 6 months. (
  • It has been long appreciated that these curative responses rely on the ability of donor-derived immune effectors to recognize and eliminate leukemic cells. (
  • Endotoxin-induced myeloid-derived suppressor cells inhibit alloimmune responses via heme oxygenase-1. (
  • These cells can differentiate into one of several subtypes, including T H 1 , T H 2 , T H 3 , T H 17 , T H 9 , or T FH , which secrete different cytokines to facilitate different types of immune responses. (
  • FL has been shown to expand distinct DC subsets in mice and to greatly augment Ag-specific T and B cell responses against soluble Ags and tumors ( 3 , 13 , 14 ). (
  • Immune responses consisted of ELISpot response in 3 recipients and positive DTH tests to WT1 peptide cocktail in 2 subjects. (
  • Upon recognizing allogeneic target cells, NK cells also secrete cytokines and chemokines that drive maturation of dendritic cells to promote cellular and humoral adaptive immune responses against the allograft. (
  • Notch signaling may play multiple important roles in peripheral T cell responses. (
  • In addition, CD40L-Tri could induce malignant B cells to become effective APCs, such that tumor-directed immune responses could be probed. (
  • CD40L-Tri-activated CLL cells effectively elicit patient CD8+ T cell responses. (
  • Furthermore, approaches of this type should help to dissect allo-specific from tumor-specific immune responses and will help to clarify, how both mechanisms are interconnected and how they can be best put in action for therapeutic purposes. (
  • Janus kinase (JAK) inhibitors have achieved positive responses in myeloproliferative neoplasms, but at the expense of decreased natural killer (NK) cell numbers and compromised function. (
  • Although JAK inhibitors can impair monocyte-derived dendritic cell (moDC) activation and function and suppress effector T-cell responses, the effects on NK cells and the relevant mechanisms remain undefined. (
  • We investigate the functional consequences of PTEN deficiency for the development of the mucosa associated lymphoid tissue, B and T cell responses. (
  • Its general tolerability, multiple proposed mechanisms of action, and familiarity have prompted IFN-α to be studied in combination with a variety of agents with potential activity against renal cell carcinoma. (
  • On April 19, 2019 , pembrolizumab was approved for use in combination with the small-molecule tyrosine kinase inhibitor axitinib for the first-line treatment of patients with advanced renal cell carcinoma. (
  • 38% ≥ 65 years), 73% were male, 79% were white and 16% Asian, 19% and 80% of patients had a baseline Karnofsky performance score of 70 to 80 and 90 to 100, and patient distribution by International Metastatic Renal Cell Carcinoma Database Consortium risk categories was 31% favorable, 56% intermediate, and 13% poor. (
  • In renal cell carcinoma , the recommended dose of pembrolizumab is 200 mg via intravenous infusion over 30 minutes every 3 weeks in combination with 5 mg of oral axitinib twice daily until disease progression, unacceptable toxicity, or for pembrolizumab, up to 24 months in patients without disease progression. (
  • Regression of Metastatic Renal-Cell Carcinoma after Nonmyeloablative, Allogeneic Peripheral-Blood Stem-Cell Transplantation," The New England Journal of Medicine, Sep. (
  • KENILWORTH, N.J.--( BUSINESS WIRE )--Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced that the U.S. Food and Drug Administration (FDA) has approved KEYTRUDA, Merck's anti-PD-1 therapy, in combination with Inlyta (axitinib), a tyrosine kinase inhibitor, for the first-line treatment of patients with advanced renal cell carcinoma (RCC). (
  • Today's approval reflects Merck's commitment to patients with cancer and further supports the use of KEYTRUDA to help improve survival outcomes for patients with advanced renal cell carcinoma. (
  • Given the aggressive nature of the disease, many patients with advanced renal cell carcinoma need additional treatment options that can help improve survival outcomes," said Dr. Brian Rini, medical oncologist at Cleveland Clinic Cancer Center and professor of medicine at the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University. (
  • Pembrolizumab in combination with axitinib offers an important new therapeutic option for physicians to consider when approaching initial treatment for patients newly diagnosed with advanced renal cell carcinoma. (
  • Dr. Childs was the first to establish that T-cells from matched donors could cure patients with metastatic renal cell carcinoma. (
  • He was the first to establish the existence of a graft-vs-solid tumor effect mediated by transplanted donor T-cells that could cure patients with metastatic renal cell carcinoma. (
  • Host and donor T cells play a critical role in this delicate balance ( 8 ). (
  • GVHD is caused by alloreactive donor T cells. (
  • GVHD prevention typically includes immunosupressive drugs that broadly suppress donor T cells. (
  • The consequences of an immune response are seen in allogeneic hematopoietic stem cell transplantation (HCT) when the peptides encoded by polymorphic genes differ between the recipient and the donor T cells. (
  • As a result, the donor T cells can target the recipients cells called graft-versus-host disease (GVHD). (
  • Unfortunately, there are also donor T cells in the HCT graft that can cause a condition called "graft versus host disease" (GVHD). (
  • ABSTRACT: The graft-vs-tumor effect is an important part of the curative potential of allogeneic transplantation. (
  • NSG™ and NSG™-SGM3 mice engrafted with allogeneic human tumors represent a valuable preclinical testing platform for immuno-oncology. (
  • Explore resources for oncology researchers such as the Mouse Tumor Biology Database. (
  • A robust immuno-oncology platform for efficacy testing of novel immunotherapies targeting T cells and myeloid cells. (
  • However, there is concern that checkpoint blockade could augment graft-versus-host disease, and very few studies have evaluated the safety of checkpoint blockade in the post-allogeneic setting. (
  • Hematopoietic stem cell transplantation therapy is potentially curative for many malignant and non-malignant hematopoietic disorders. (
  • Stem cells are collected (harvested) before conditioning therapy starts and are usually frozen until it is time for use. (
  • After conditioning therapy, stem cells are infused into the bloodstream (usually between 30 and 60 minutes), akin to a blood transfusion procedure. (
  • As potential therapy, NK cells, including adaptive NK cells, can be adoptively transferred with, or without, agents such as IL-15 that promote NK cell survival. (
  • The bottom line is that transplantation today is a much more effective therapy and a therapy we are able to apply to many more people. (
  • Here, as well, we need to evaluate things like maintenance therapy in the minimal residual disease state, and augmentation of antitumor effects using tumor-specific T cells or natural killer cells. (
  • Immune checkpoint inhibition (ICI) became one of the major breakthroughs in cancer treatment over the past decade and entered into therapy within standard oncohematology practice. (
  • CONCLUSIONS AND PERSPECTIVES: Present and future challenges in this field are represented by the expansion of true human stem cells without maturation, to extend this strategy to allogeneic stem cell transplantation as well as the manipulation of cycling of primitive progenitors for gene therapy programs. (
  • This strategy promises to extend the use of NK cells in cancer therapy beyond allogeneic mismatched hematopoietic stem cell transplantation. (
  • Although this therapy has shown promising results we have only a remote understanding of how to utilize T and NK cells to their full potential. (
  • KENILWORTH, N.J.--( BUSINESS WIRE )-- Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced that the pivotal Phase 3 KEYNOTE-042 trial evaluating KEYTRUDA, Merck's anti-PD-1 therapy, as monotherapy for the first-line treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC, including nonsquamous or squamous histologies) met its primary endpoint of overall survival (OS). (
  • Patients had no EGFR or ALK genomic tumor aberrations and had not previously received systemic therapy for advanced disease. (
  • The choice of therapy depends upon the location and grade of the tumor and the stage of the disease, as well as the general state of the patient (performance status). (
  • Radiation therapy (also called radiotherapy, X-ray therapy, or irradiation) is the use of ionizing radiation to kill cancer cells and shrink tumors. (
  • Radiation therapy injures or destroys cells in the area being treated (the "target tissue") by damaging their genetic material, making it impossible for these cells to continue to grow and divide. (
  • The goal of radiation therapy is to damage as many cancer cells as possible, while limiting harm to nearby healthy tissue. (
  • Single dose versus multiple doses of rituximab for preemptive therapy of Epstein-Barr virus reactivation after hematopoietic cell transplantation. (
  • CAR-T cell therapy involves engineering immune cells (from a patient or a donor) to recognize and prompt the body's immune system to fight cancerous tumors. (
  • Our study provides 1 of the first attempts to apply tumor-specific vaccine therapy to the allogeneic setting. (
  • Tumor removal surgeries have been documented in ancient Egypt, hormone therapy and radiation therapy were developed in the late 19th century. (
  • Vascular and haematopoietic stem cells: novel targets for anti-angiogenesis therapy? (
  • Human Gene Therapy is commemorating its 25th anniversary by bestowing this honor on the leading 12 Pioneers in the field of cell and gene therapy selected by a blue ribbon panel* and publishing a Pioneer Perspective by each of the award recipients. (
  • In " Gene Modified Cells for Stem Cell Transplantation and Cancer Therapy ," Dr. Brenner recounts the highlights of his career to date. (
  • Malcolm has been driving the field of cell-based gene therapy forward since its infancy. (
  • The blue ribbon panel of leaders in cell and gene therapy, led by Chair Mary Collins, PhD, MRC Centre for Medical Molecular Virology, University College London selected the Pioneer Award recipients. (
  • Human Gene Therapy , the official journal of the European Society of Gene and Cell Therapy, British Society for Gene and Cell Therapy, French Society of Cell and Gene Therapy, German Society of Gene Therapy, and five other gene therapy societies, is an authoritative peer-reviewed journal published monthly in print and online. (
  • 5. Sharpe M, Mount N. Genetically modified T cells in cancer therapy: opportunities and challenges. (
  • Novartis personalized cell therapy CTL019 receives FDA breakthrough therapy designation. (
  • Phase 1 Results of ZUMA1: a multicenter study of KTE-C19 Anti-CD19 CAR T cell therapy in refractory aggressive lymphoma. (
  • Leading scientists therefore assume that every seventh person will need a therapy based on stem cells in the course of their lives in the near future. (
  • In this study, BCG-unresponsive high-risk NMIBC was defined as persistent disease despite adequate BCG therapy, disease recurrence after an initial tumor-free state following adequate BCG therapy, or T1 disease following a single induction course of BCG. (
  • The patient will then be treated and at the time high dose therapy for AHSCT is administered the cell culture will be initiated in a central lab. (
  • In this prospective study we characterized graft composition of T- and NK cell subsets in 88 recipients of peripheral blood stem cell grafts with multicolor flowcytometry. (
  • Now, several immunosuppressive agents are used for allogeneic transplantation recipients. (
  • 1-7] A number of factors, including patient disease status, age, conditioning regimen, and (for allogeneic recipients) type of graft-vs-host disease prophylaxis, influence the probability of survival after transplantation. (
  • Recently, his team has discovered that exposing tumors to proteasome inhibitors sensitizes them to NK cells through expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). (
  • Strategies including antibody-directed approaches, stem cell transplantation, immunomodulatory drugs, immune checkpoint inhibitors, CAR T cells, and vaccines have demonstrated particular success in controlling and even eradicating hematological cancers. (
  • These results demonstrate that ruxolitinib's nonselective inhibition of JAK1/2 results in profound NK-cell dysfunction by blocking downstream pSTAT5, hence providing a persuasive rationale for the development of selective JAK2 inhibitors for immunotherapeutic applications. (
  • Although the mechanism of action of these cytokines remains to be fully elucidated, antitumor effects in murine models have been linked to the direct killing of tumor cells by activated T cells and natural killer cells, as well as to antiangiogenic effects. (
  • STATE OF ART: Over the last decade, recombinant DNA technology has allowed the large scale production of cytokines controlling the proliferation and differentiation of hemo-lymphopoietic cells. (
  • This expansion occurs predominantly in the CD8+ memory T cell population, which in comparison with naive T cells is more responsive to cytokines (IL-2, IL-15, and IL-17) and previously encountered pathogens (such as reactivated viruses), and less dependent upon recognition of self MHC-peptide complexes for survival ( 10 ). (
  • Once activated, they divide rapidly and secrete small proteins called cytokines that regulate or assist in the active immune response. (
  • In humans, the monocyte-derived CD11c + DCs induce T cells to produce Th1 cytokines in vitro, whereas the CD11c − plasmacytoid T cell-derived DCs elicit the production of Th2 cytokines. (
  • 6 directly killing tumor cells through the Fas and perforin pathways, but also indirectly contributing to tumor lysis through the secretion of cytokines. (
  • Following recognition, T cells either directly lyse their targets by secreting powerful perforins and granzymes, or orchestrate a more potent immune response by secreting inflammatory cytokines and chemokines. (
  • CD8+ T cells are also able to utilize small signalling proteins, known as cytokines , to recruit other cells when mounting an immune response. (
  • Using common γ c cytokines and distinct human dendritic cell (DC) subtypes, we compared the effects of a JAK2-specific (TG101348) with a less selective JAK1/2 (ruxolitinib) inhibitor on NK-cell activation and function. (
  • NK cells, monocytes, and dendritic cells) in these patients. (
  • Dendritic cells (DCs) have a unique ability to stimulate naive T cells. (
  • The Xbox binding protein 1 (XBP-1) transcription factor is a critical regulator of endoplasmic reticulum (ER) stress in dendritic cells (DC) and coordinates inflammasome activation via NLRP3 allowing DCs to promote Th17 differentiation that is relevant to graft-versus-host disease (GVHD). (
  • The TCR alpha/beta/CD19-depleted HPCs contain high amounts of natural killer (NK) cells, gamma/delta T-cells, CD34+ stem cells, monocytes, and dendritic cells (DCs), while devoid of alpha/beta T cells and CD19-positive B cells. (
  • and IL-17) and failed to cause GVHD, suggesting that the Notch pathway increased on the surface of a subset of recipient dendritic cells (DCs) during GVHD induction. (
  • Allogeneic HSC donors must have a tissue (HLA) type that matches the recipient and, in addition, the recipient requires immunosuppressive medications. (
  • Peripheral NK cells from 30 and 10 patients who reactivated respectively CMV and AdV are prospectively studied (extensive phenotyping and functional studies before and after administration of anti viral drugs) and compared with 30 allotransplanted patients who didn't reactivate CMV in a pair analysis, and 30 healthy donors serologically + for CMV. (
  • The state of NK cells differentiation and maturation will be assessed by the analyze of thoses phenotypic markers and will be compared with healthy donors. (
  • Due to the high selectivity of the gene-modified NK cells for their tumor targets, NK cells from fully matched donors as well as autologous NK cells can be used. (
  • The B-Cell Lymphoma Moon Shot is revolutionizing the conventional medical research approach to rapidly translate findings into patient treatment options and develop personalized therapeutic strategies. (
  • Immunomodulatory chemotherapies, such as lenalidomide, are also thought to provide therapeutic benefit via mechanisms due in part to stimulation of T-cell and/or natural killer (NK) cell activity against myeloma cells ( 3 ). (
  • Various attempts have been made in recent years to expand and manipulate these cells in order to increase their therapeutic potential. (
  • This "graft-vs-solid tumor" effect, published in the New England Journal of Medicine in 2000, defined a new therapeutic application for allogeneic hematopoietic stem cell transplantation. (
  • PROHEMA ® is a pharmacologically-modulated, cord blood-derived hematopoietic stem cell (HSC) therapeutic. (
  • The potential of stem cells therefore is enormous and already provides for entirely new therapeutic options in the field of individualized, regenerative medicine. (
  • The potential of stem cells is enormous and provides access to entirely new therapeutic options in the field of individualized, regenerative medicine. (
  • Blood cancers multiply uncontrollably, hindering the growth of these cells. (
  • Dr Colin Phipps Diong, Parkway Cancer Centre's new consultant specialising in lymphoma and blood cancers, and haematopoietic stem cell transplantation, explains haematopoietic stem cell transplantation. (
  • Results of the study demonstrate that infusion of anti-CD19 CAR-T cells-targeted DLI-holds great promise in treating B-cell cancers recurring post transplantation. (
  • It is now believed that many nascent cancers never proliferate to life-threatening proportions because of routine surveillance by the immune system. (
  • Dr. Childs's translational research program is focused on finding ways to adapt and enhance immune cells to attack even the most entrenched cancers. (
  • Work in his lab has also focused on developing novel natural killer cell-based strategies to prevent graft-versus-host disease (GVHD) and to treat advanced cancers. (
  • Many cancers can be diagnosed by inserting a small needle into the tumor mass and withdrawing cells for examination under a microscope. (
  • Because many cancers dedifferentiate to a stem cell-like state, refined knowledge about how KZNFs act to finely modulate transcriptional control may prove essential for the development of new cancer drugs. (
  • Therefore, sustainment of long-term remission is crucial, using either drug maintenance treatment or by boosting or prolonging an immune response. (
  • Lack of persistent remission following initial recovery in patients with type 1 diabetes treated with autologous peripheral blood stem cell transplantation. (
  • CHL exquisite sensitivity to PD-1 blockade relies on lymphoma cell genetic alterations and particular tumor microenvironment (TME) inflammatory phenotype. (
  • It is expressed in mature B-cells and Burkitt's lymphoma. (
  • Hodgkin lymphoma (HL) is a rare B-cell derived lymphoid malignancy. (
  • While some of the immune cells present in lymphoma have effector function, the immune system is unable to eradicate the malignant clone. (
  • Diffuse large B-cell lymphoma (DLBCL) is by far the most common, accounting for 31% of cases. (
  • Allogeneic stem cell transplantation for patients with relapsed or refractory T-cell lymphoma: efficacy of lymphoma-directed conditioning against advanced disease. (
  • Diffuse large B-cell lymphoma is a subcategory of non-Hodgkins lymphoma that commonly affects the stomach, thyroid, parotid glands, and lungs. (
  • We present the case of an enlarging chest wall mass with an associated lymphomatous pleural effusion found to be an unusual presentation of diffuse large B-cell lymphoma. (
  • Chrissy A. Navejar and Michael J. Morris, " Diffuse Large B-Cell Lymphoma Presenting as an Anterior Chest Wall Mass: A Case Report and Literature Review", Current Respiratory Medicine Reviews (2009) 5: 239. (
  • Variation in the gastrointestinal microbiota after hematopoietic cell transplantation has been associated with acute graft-versus-host disease (aGVHD). (
  • Biology of Blood and Marrow Transplantation , 22 (12), 2149-2154. (
  • Dr. Childs and his colleagues have developed and implemented a protocol that combines two stem cell sources: transplanted umbilical cord blood and cells purified from a partially matched relative (parent, child, or un-matched sibling) to treat patients with aplastic anemia that are at high risk of graft rejection. (
  • The functional properties of both hematopoietic stem cells and T cells are critical determinants of patient outcomes following allogeneic umbilical cord blood transplantation," commented Pratik Multani, M.D., M.S., Chief Medical Officer of Fate Therapeutics. (
  • Store umbilical cord blood with VitaPlus to secure the young and viable stem cells right after the birth. (
  • Store stem cells from umbilical cord and umbilical tissue and benefit from the full potential of the umbilical cord. (
  • ALT-803 lost its antimyeloma activity in tumor-bearing IFN-γ knockout mice but retained the ability to promote CD8 + CD44 high memory T-cell proliferation, indicating that ALT-803-mediated stimulation of CD8 + CD44 high memory T cells is IFN-γ-independent. (
  • Grllich(6) et al and the investigators study(7) both found that ATG can inhibit the proliferation and induce high level of apoptosis in the human lymphoblastic cell lines, such as Jurkat, Daudi, DG-75 , and myeloblastic cell lines K562, HL-60, KG1, and U937. (
  • Targeting TAAs that drive the proliferation of the malignant clone will not only contribute to the reduction of the disease burden, but may eliminate the underlying malignant clone/stem cell, which must ultimately be eradicated for achieving cure. (
  • The proliferation of LNCaP cells was also investigated after the knockdown CXCR5. (
  • The methods comprise administering to a donor an amount of thrombopoietin sufficient to stimulate proliferation of cells of the myeloid lineage, collecting cells from the donor, and administering the collected cells to a recipient patient. (
  • These cells then undergo a round of proliferation and begin to re-arrange TCRα locus. (
  • Although the mechanism of action has not been elucidated, following subcutaneous administration, CD44 targeted agent SPL-108 binds to CD44 and prevents the activation of various CD44-mediated signal transduction pathways, which may lead to reduced proliferation of CD44-expressing tumor stem cells. (
  • it plays a key role in the proliferation, migration and survival of tumor cells. (
  • PTLD results from the uncontrolled neoplastic proliferation of lymphoid or plasmacytic cells. (
  • Only NK-cell proliferation stimulated by moDCs resisted ruxolitinib treatment. (
  • Hematopoietic stem cells (HSCs) mostly reside in the BM, where they undergo proliferation and multi-lineage differentiation, giving rise to mature leukocytes and erythrocytes, which are released in turn to the blood in order to carry out their function ( Orkin and Zon, 2008 ). (
  • While, several studies reported that HMA induce the expression of Foxp3 in activated T cells generating functional Tregs with suppressor properties. (
  • To assess metabolic control in patients with newly diagnosed type 1 diabetes mellitus who underwent immunoablation followed by autologous peripheral blood stem cell transplantation (APBSCT) as a treat. (
  • BPH-1 and peripheral blood mononuclear cells (PBMCs) were co-cultured in Transwell chambers, and human normal prostate (NP) tissues, BPH tissues and PCa tissues were collected. (
  • We have shown that specific AML-reactive T cells can be generated and expanded from primary cultures of mononuclear cells from all newly diagnosed patients with AML using a novel cell culture method employing sequential modulation of growth factors. (
  • Mononuclear cells containing AML blasts and normal T cells will be cryopreserved. (
  • The transplanted cells kill any remaining cancer cells and restore the patient's immune system. (
  • We review and discuss the utility of T reg cells for treatment of cancer. (
  • More recently, evidence has accumulated that T cells also help control many different types of tumors, at least in subpopulations of patients with cancer. (
  • The STEM PACE trial is a single center, phase II study to evaluate adjuvant allogeneic hematopoietic stem cell transplantation in pancreatic cancer after surgical resection. (
  • Lung cancer, which forms in the tissues of the lungs, usually within cells lining the air passages, is the leading cause of cancer death worldwide. (
  • The two main types of lung cancer are non-small cell and small cell. (
  • Superresolution image of a group of killer T cells (green and red) surrounding a cancer cell (blue, center). (
  • In the Halstedian model of cancer progression, tumors grow locally, then spread to the lymph nodes, then to the rest of the body. (
  • A single cancer cell is invisible to the naked eye but can regrow into a new tumor, a process called recurrence. (
  • For this reason, the pathologist will examine the surgical specimen to determine if a margin of healthy tissue is present, thus decreasing the chance that microscopic cancer cells are left in the patient. (
  • Although radiation damages both cancer cells and normal cells, most normal cells can recover from the effects of radiation and function properly. (
  • This webinar highlights recent advances and future directions using xenografted humanized NSG™ mice with functional human immune cells, to evaluate cancer immunotherapies. (
  • JAX researchers report in Cancer Cell further insight into yet another way extrachromosomal, circular DNA (ecDNA) may. (
  • cancer cells from dividing so they stop growing or die. (
  • cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. (
  • Bryostatin 1 may help rituximab kill more cancer cells by making them more sensitive to the drug. (
  • Combining more than one drug may kill more cancer cells. (
  • Cancer immunologist Alan Houghton studies the immune response to cancer, immune recognition of self and mutated molecules, and development of new immunotherapies. (
  • Immunologist Ming Li studies mechanisms of immune regulation, and their relevance to diseases including cancer. (
  • Immunologist Justin Perry investigates homeostatic apoptotic cell clearance and how this process is exploited during cancer development and progression. (
  • Immunologist Joseph Sun investigates the natural killer cell response against infection and cancer. (
  • Examples of surgical procedures for cancer include mastectomy for breast cancer, prostatectomy for prostate cancer, and lung cancer surgery for non-small cell lung cancer. (
  • These same self-tolerant cells are co-opted by cancer cells to prevent the recognition of, and an immune response against, tumour cells. (
  • Expression of CD47, and its interaction with SIRPa, leads to the inhibition of macrophage activation and protects cancer cells from phagocytosis, which allows cancer cells to proliferate. (
  • Allogeneic hematopoietic stem cell transplantation represents the most striking example that immune cells can destroy tumor cells and cure cancer. (
  • We also work towards devising strategies to exploit the GI-driving pathways as vulnerabilities to selectively kill cancer cells. (
  • Subsequently, his group characterized the immune mechanisms mediating this effect and in experiments using allogeneic T-cells from responding patients, discovered a novel human endogenous retrovirus expressed in kidney cancer that serves as a target for human immune cells. (
  • His laboratory then characterized the molecular mechanisms leading to the selective transcription of this provirus in the clear cell subtype of kidney cancer. (
  • A major focus of the Childs laboratory is on the potentiation of natural killer (NK) cells, which are the key immune cell effectors of cancer cell death. (
  • Immunotherapeutic strategies leveraging the immune system's antitumor activity have become a mainstay of cancer treatment. (
  • Stem cells have been applied to treat hematopoietic disorders, diseases of the immune system and mainly cancer since 1988. (
  • Non-small cell lung cancer (NSCLC) is a particularly aggressive type of lung cancer, and mesothelioma is an equally aggressive cancer of the lining of the lung. (
  • The approval was based on data from KEYNOTE-057 ( NCT02625961 ), a multicenter, open-label, single-arm trial in 96 patients with BCG-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy. (
  • The focus of our research for the past decade has been the development of treatment strategies to modulate the immune system of patients with cancer. (