Substances that are recognized by the immune system and induce an immune reaction.
Proteins, glycoprotein, or lipoprotein moieties on surfaces of tumor cells that are usually identified by monoclonal antibodies. Many of these are of either embryonic or viral origin.
Substances elaborated by bacteria that have antigenic activity.
Antigens on surfaces of cells, including infectious or foreign cells or viruses. They are usually protein-containing groups on cell membranes or walls and may be isolated.
Substances elaborated by viruses that have antigenic activity.
Molecular products metabolized and secreted by neoplastic tissue and characterized biochemically in cells or body fluids. They are indicators of tumor stage and grade as well as useful for monitoring responses to treatment and predicting recurrence. Many chemical groups are represented including hormones, antigens, amino and nucleic acids, enzymes, polyamines, and specific cell membrane proteins and lipids.
Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.
The total amount (cell number, weight, size or volume) of tumor cells or tissue in the body.
A cell line derived from cultured tumor cells.
Polyomavirus antigens which cause infection and cellular transformation. The large T antigen is necessary for the initiation of viral DNA synthesis, repression of transcription of the early region and is responsible in conjunction with the middle T antigen for the transformation of primary cells. Small T antigen is necessary for the completion of the productive infection cycle.
Any part or derivative of any protozoan that elicits immunity; malaria (Plasmodium) and trypanosome antigens are presently the most frequently encountered.
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.
Antibodies produced by a single clone of cells.
Experimentally induced new abnormal growth of TISSUES in animals to provide models for studying human neoplasms.
Those proteins recognized by antibodies from serum of animals bearing tumors induced by viruses; these proteins are presumably coded for by the nucleic acids of the same viruses that caused the neoplastic transformation.
A glycoprotein that is secreted into the luminal surface of the epithelia in the gastrointestinal tract. It is found in the feces and pancreaticobiliary secretions and is used to monitor the response to colon cancer treatment.
A malignant kidney tumor, caused by the uncontrolled multiplication of renal stem (blastemal), stromal (STROMAL CELLS), and epithelial (EPITHELIAL CELLS) elements. However, not all three are present in every case. Several genes or chromosomal areas have been associated with Wilms tumor which is usually found in childhood as a firm lump in a child's side or ABDOMEN.
Substances of fungal origin that have antigenic activity.
The major group of transplantation antigens in the mouse.
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.
Any part or derivative of a helminth that elicits an immune reaction. The most commonly seen helminth antigens are those of the schistosomes.
Genes that inhibit expression of the tumorigenic phenotype. They are normally involved in holding cellular growth in check. When tumor suppressor genes are inactivated or lost, a barrier to normal proliferation is removed and unregulated growth is possible.
Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER.
A usually small, slow-growing neoplasm composed of islands of rounded, oxyphilic, or spindle-shaped cells of medium size, with moderately small vesicular nuclei, and covered by intact mucosa with a yellow cut surface. The tumor can occur anywhere in the gastrointestinal tract (and in the lungs and other sites); approximately 90% arise in the appendix. It is now established that these tumors are of neuroendocrine origin and derive from a primitive stem cell. (From Stedman, 25th ed & Holland et al., Cancer Medicine, 3d ed, p1182)
Nuclear antigen with a role in DNA synthesis, DNA repair, and cell cycle progression. PCNA is required for the coordinated synthesis of both leading and lagging strands at the replication fork during DNA replication. PCNA expression correlates with the proliferation activity of several malignant and non-malignant cell types.
Molecules on the surface of T-lymphocytes that recognize and combine with antigens. The receptors are non-covalently associated with a complex of several polypeptides collectively called CD3 antigens (ANTIGENS, CD3). Recognition of foreign antigen and the major histocompatibility complex is accomplished by a single heterodimeric antigen-receptor structure, composed of either alpha-beta (RECEPTORS, ANTIGEN, T-CELL, ALPHA-BETA) or gamma-delta (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA) chains.
Tumors whose cells possess secretory granules and originate from the neuroectoderm, i.e., the cells of the ectoblast or epiblast that program the neuroendocrine system. Common properties across most neuroendocrine tumors include ectopic hormone production (often via APUD CELLS), the presence of tumor-associated antigens, and isozyme composition.
A subclass of HLA-D antigens that consist of alpha and beta chains. The inheritance of HLA-DR antigens differs from that of the HLA-DQ ANTIGENS and HLA-DP ANTIGENS.
Proteins that are normally involved in holding cellular growth in check. Deficiencies or abnormalities in these proteins may lead to unregulated cell growth and tumor development.
Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain.
Established cell cultures that have the potential to propagate indefinitely.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
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.
A group of antigens that includes both the major and minor histocompatibility antigens. The former are genetically determined by the major histocompatibility complex. They determine tissue type for transplantation and cause allograft rejections. The latter are systems of allelic alloantigens that can cause weak transplant rejection.
The milieu surrounding neoplasms consisting of cells, vessels, soluble factors, and molecules, that can influence and be influenced by, the neoplasm's growth.
Sites on an antigen that interact with specific antibodies.
A glycoprotein that is a kallikrein-like serine proteinase and an esterase, produced by epithelial cells of both normal and malignant prostate tissue. It is an important marker for the diagnosis of prostate cancer.
Experimentally induced mammary neoplasms in animals to provide a model for studying human BREAST NEOPLASMS.
An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.
Carbohydrate antigens expressed by malignant tissue. They are useful as tumor markers and are measured in the serum by means of a radioimmunoassay employing monoclonal antibodies.
Large, transmembrane, non-covalently linked glycoproteins (alpha and beta). Both chains can be polymorphic although there is more structural variation in the beta chains. The class II antigens in humans are called HLA-D ANTIGENS and are coded by a gene on chromosome 6. In mice, two genes named IA and IE on chromosome 17 code for the H-2 antigens. The antigens are found on B-lymphocytes, macrophages, epidermal cells, and sperm and are thought to mediate the competence of and cellular cooperation in the immune response. The term IA antigens used to refer only to the proteins encoded by the IA genes in the mouse, but is now used as a generic term for any class II histocompatibility antigen.
A malignant epithelial tumor with a glandular organization.
The transfer of a neoplasm from one organ or part of the body to another remote from the primary site.
IMMUNOGLOBULINS on the surface of B-LYMPHOCYTES. Their MESSENGER RNA contains an EXON with a membrane spanning sequence, producing immunoglobulins in the form of type I transmembrane proteins as opposed to secreted immunoglobulins (ANTIBODIES) which do not contain the membrane spanning segment.
A pathologic process consisting of the proliferation of blood vessels in abnormal tissues or in abnormal positions.
A specific HLA-A surface antigen subtype. Members of this subtype contain alpha chains that are encoded by the HLA-A*02 allele family.
Immunologic techniques based on the use of: (1) enzyme-antibody conjugates; (2) enzyme-antigen conjugates; (3) antienzyme antibody followed by its homologous enzyme; or (4) enzyme-antienzyme complexes. These are used histologically for visualizing or labeling tissue specimens.
Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.
Transplantation between animals of different species.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
The lipopolysaccharide-protein somatic antigens, usually from gram-negative bacteria, important in the serological classification of enteric bacilli. The O-specific chains determine the specificity of the O antigens of a given serotype. O antigens are the immunodominant part of the lipopolysaccharide molecule in the intact bacterial cell. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of IgG, for example, IgG1, IgG2A, and IgG2B.
A trisaccharide antigen expressed on glycolipids and many cell-surface glycoproteins. In the blood the antigen is found on the surface of NEUTROPHILS; EOSINOPHILS; and MONOCYTES. In addition, CD15 antigen is a stage-specific embryonic antigen.
Differentiation antigens found on thymocytes and on cytotoxic and suppressor T-lymphocytes. CD8 antigens are members of the immunoglobulin supergene family and are associative recognition elements in MHC (Major Histocompatibility Complex) Class I-restricted interactions.
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.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
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.
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.
Tumors or cancer of the COLON.
Complex of at least five membrane-bound polypeptides in mature T-lymphocytes that are non-covalently associated with one another and with the T-cell receptor (RECEPTORS, ANTIGEN, T-CELL). The CD3 complex includes the gamma, delta, epsilon, zeta, and eta chains (subunits). When antigen binds to the T-cell receptor, the CD3 complex transduces the activating signals to the cytoplasm of the T-cell. The CD3 gamma and delta chains (subunits) are separate from and not related to the gamma/delta chains of the T-cell receptor (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA).
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.
Elements of limited time intervals, contributing to particular results or situations.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
All tumors in the GASTROINTESTINAL TRACT arising from mesenchymal cells (MESODERM) except those of smooth muscle cells (LEIOMYOMA) or Schwann cells (SCHWANNOMA).
In vivo methods of screening investigative anticancer drugs, biologic response modifiers or radiotherapies. Human tumor tissue or cells are transplanted into mice or rats followed by tumor treatment regimens. A variety of outcomes are monitored to assess antitumor effectiveness.
Serological reactions in which an antiserum against one antigen reacts with a non-identical but closely related antigen.
Membrane glycoproteins consisting of an alpha subunit and a BETA 2-MICROGLOBULIN beta subunit. In humans, highly polymorphic genes on CHROMOSOME 6 encode the alpha subunits of class I antigens and play an important role in determining the serological specificity of the surface antigen. Class I antigens are found on most nucleated cells and are generally detected by their reactivity with alloantisera. These antigens are recognized during GRAFT REJECTION and restrict cell-mediated lysis of virus-infected cells.
Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill.
Polymorphic class I human histocompatibility (HLA) surface antigens present on almost all nucleated cells. At least 20 antigens have been identified which are encoded by the A locus of multiple alleles on chromosome 6. They serve as targets for T-cell cytolytic responses and are involved with acceptance or rejection of tissue/organ grafts.
The property of antibodies which enables them to react with some ANTIGENIC DETERMINANTS and not with others. Specificity is dependent on chemical composition, physical forces, and molecular structure at the binding site.
Tumors or cancer of the LIVER.
Sets of cell surface antigens located on BLOOD CELLS. They are usually membrane GLYCOPROTEINS or GLYCOLIPIDS that are antigenically distinguished by their carbohydrate moieties.
Those hepatitis B antigens found on the surface of the Dane particle and on the 20 nm spherical and tubular particles. Several subspecificities of the surface antigen are known. These were formerly called the Australia antigen.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
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.
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.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
A sarcoma derived from deep fibrous tissue, characterized by bundles of immature proliferating fibroblasts with variable collagen formation, which tends to invade locally and metastasize by the bloodstream. (Stedman, 25th ed)
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
Experimentally induced neoplasms of CONNECTIVE TISSUE in animals to provide a model for studying human SARCOMA.
Tumors or cancer of the OVARY. These neoplasms can be benign or malignant. They are classified according to the tissue of origin, such as the surface EPITHELIUM, the stromal endocrine cells, and the totipotent GERM CELLS.
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.
Tumors or cancer of the SKIN.
Tumors or cancers of the KIDNEY.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
A CELL CYCLE and tumor growth marker which can be readily detected using IMMUNOCYTOCHEMISTRY methods. Ki-67 is a nuclear antigen present only in the nuclei of cycling cells.
Methods which attempt to express in replicable terms the extent of the neoplasm in the patient.
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.
Experimentally induced tumor that produces MELANIN in animals to provide a model for studying human MELANOMA.
A transplantable, poorly differentiated malignant tumor which appeared originally as a spontaneous breast carcinoma in a mouse. It grows in both solid and ascitic forms.
Human immune-response or Class II antigens found mainly, but not exclusively, on B-lymphocytes and produced from genes of the HLA-D locus. They are extremely polymorphic families of glycopeptides, each consisting of two chains, alpha and beta. This group of antigens includes the -DR, -DQ and -DP designations, of which HLA-DR is most studied; some of these glycoproteins are associated with certain diseases, possibly of immune etiology.
Vaccines or candidate vaccines designed to prevent or treat cancer. Vaccines are produced using the patient's own whole tumor cells as the source of antigens, or using tumor-specific antigens, often recombinantly produced.
Deliberate stimulation of the host's immune response. ACTIVE IMMUNIZATION involves administration of ANTIGENS or IMMUNOLOGIC ADJUVANTS. PASSIVE IMMUNIZATION involves administration of IMMUNE SERA or LYMPHOCYTES or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow).
55-kDa antigens found on HELPER-INDUCER T-LYMPHOCYTES and on a variety of other immune cell types. CD4 antigens are members of the immunoglobulin supergene family and are implicated as associative recognition elements in MAJOR HISTOCOMPATIBILITY COMPLEX class II-restricted immune responses. On T-lymphocytes they define the helper/inducer subset. CD4 antigens also serve as INTERLEUKIN-15 receptors and bind to the HIV receptors, binding directly to the HIV ENVELOPE PROTEIN GP120.
Molecules on the surface of B- and T-lymphocytes that recognize and combine with specific antigens.
DNA present in neoplastic tissue.
The phenomenon of target cell destruction by immunologically active effector cells. It may be brought about directly by sensitized T-lymphocytes or by lymphoid or myeloid "killer" cells, or it may be mediated by cytotoxic antibody, cytotoxic factor released by lymphoid cells, or complement.
The processes triggered by interactions of ANTIBODIES with their ANTIGENS.
The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES.
Proteins prepared by recombinant DNA technology.
An encapsulated lymphatic organ through which venous blood filters.
Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses.
Benign and malignant central nervous system neoplasms derived from glial cells (i.e., astrocytes, oligodendrocytes, and ependymocytes). Astrocytes may give rise to astrocytomas (ASTROCYTOMA) or glioblastoma multiforme (see GLIOBLASTOMA). Oligodendrocytes give rise to oligodendrogliomas (OLIGODENDROGLIOMA) and ependymocytes may undergo transformation to become EPENDYMOMA; CHOROID PLEXUS NEOPLASMS; or colloid cysts of the third ventricle. (From Escourolle et al., Manual of Basic Neuropathology, 2nd ed, p21)
Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation.
Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition. (From Last, Dictionary of Epidemiology, 2d 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.
The production of ANTIBODIES by proliferating and differentiated B-LYMPHOCYTES under stimulation by ANTIGENS.
Antigens expressed primarily on the membranes of living cells during sequential stages of maturation and differentiation. As immunologic markers they have high organ and tissue specificity and are useful as probes in studies of normal cell development as well as neoplastic transformation.
A melanosome-specific protein that plays a role in the expression, stability, trafficking, and processing of GP100 MELANOMA ANTIGEN, which is critical to the formation of Stage II MELANOSOMES. The protein is used as an antigen marker for MELANOMA cells.
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.
Antigens of the virion of the HEPATITIS B VIRUS or the Dane particle, its surface (HEPATITIS B SURFACE ANTIGENS), core (HEPATITIS B CORE ANTIGENS), and other associated antigens, including the HEPATITIS B E ANTIGENS.
Tumors or cancer of the PANCREAS. Depending on the types of ISLET CELLS present in the tumors, various hormones can be secreted: GLUCAGON from PANCREATIC ALPHA CELLS; INSULIN from PANCREATIC BETA CELLS; and SOMATOSTATIN from the SOMATOSTATIN-SECRETING CELLS. Most are malignant except the insulin-producing tumors (INSULINOMA).
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).
The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis.
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.
Glycoproteins expressed on cortical thymocytes and on some dendritic cells and B-cells. Their structure is similar to that of MHC Class I and their function has been postulated as similar also. CD1 antigens are highly specific markers for human LANGERHANS CELLS.
A carcinoma derived from stratified SQUAMOUS EPITHELIAL CELLS. It may also occur in sites where glandular or columnar epithelium is normally present. (From Stedman, 25th ed)
Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).
A costimulatory ligand expressed by ANTIGEN-PRESENTING CELLS that binds to CTLA-4 ANTIGEN with high specificity and to CD28 ANTIGEN with low specificity. The interaction of CD80 with CD28 ANTIGEN provides a costimulatory signal to T-LYMPHOCYTES, while its interaction with CTLA-4 ANTIGEN may play a role in inducing PERIPHERAL TOLERANCE.
Immunoglobulins produced in a response to BACTERIAL ANTIGENS.
Class I human histocompatibility (HLA) surface antigens encoded by more than 30 detectable alleles on locus B of the HLA complex, the most polymorphic of all the HLA specificities. Several of these antigens (e.g., HLA-B27, -B7, -B8) are strongly associated with predisposition to rheumatoid and other autoimmune disorders. Like other class I HLA determinants, they are involved in the cellular immune reactivity of cytolytic T lymphocytes.
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.
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.
Serum that contains antibodies. It is obtained from an animal that has been immunized either by ANTIGEN injection or infection with microorganisms containing the antigen.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
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.
A rare but highly lethal childhood tumor found almost exclusively in infants. Histopathologically, it resembles RHABDOMYOSARCOMA but the tumor cells are not of myogenic origin. Although it arises primarily in the kidney, it may be found in other parts of the body. The rhabdoid cytomorphology is believed to be the expression of a very primitive malignant cell. (From Holland et al., Cancer Medicine, 3d ed, p2210)
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
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.
Experimental transplantation of neoplasms in laboratory animals for research purposes.
A general term for various neoplastic diseases of the lymphoid tissue.
A group of genetically identical cells all descended from a single common ancestral cell by mitosis in eukaryotes or by binary fission in prokaryotes. Clone cells also include populations of recombinant DNA molecules all carrying the same inserted sequence. (From King & Stansfield, Dictionary of Genetics, 4th ed)
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.
Tumors or cancer of the human BREAST.
They are oval or bean shaped bodies (1 - 30 mm in diameter) located along the lymphatic system.
Tumors or cancer of the MAMMARY GLAND in animals (MAMMARY GLANDS, ANIMAL).
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.
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.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.
Manifestations of the immune response which are mediated by antigen-sensitized T-lymphocytes via lymphokines or direct cytotoxicity. This takes place in the absence of circulating antibody or where antibody plays a subordinate role.
Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios.
The sum of the weight of all the atoms in a molecule.
Tumors or cancer located in bone tissue or specific BONES.
A member of the tumor necrosis factor receptor superfamily with specificity for CD40 LIGAND. It is found on mature B-LYMPHOCYTES and some EPITHELIAL CELLS, lymphoid DENDRITIC CELLS. Evidence suggests that CD40-dependent activation of B-cells is important for generation of memory B-cells within the germinal centers. Mutations of the gene for CD40 antigen result in HYPER-IGM IMMUNODEFICIENCY SYNDROME, TYPE 3. Signaling of the receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.
A species of POLYOMAVIRUS originally isolated from Rhesus monkey kidney tissue. It produces malignancy in human and newborn hamster kidney cell cultures.
The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.
A primary malignant neoplasm of epithelial liver cells. It ranges from a well-differentiated tumor with EPITHELIAL CELLS indistinguishable from normal HEPATOCYTES to a poorly differentiated neoplasm. The cells may be uniform or markedly pleomorphic, or form GIANT CELLS. Several classification schemes have been suggested.
A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures.
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.
Antigens associated with specific proteins of the human adult T-cell immunodeficiency virus (HIV); also called HTLV-III-associated and lymphadenopathy-associated virus (LAV) antigens.
Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.
Differentiation antigens expressed on B-lymphocytes and B-cell precursors. They are involved in regulation of B-cell proliferation.
The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)
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 determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.
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.
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.
A cytologic technique for measuring the functional capacity of tumor stem cells by assaying their activity. It is used primarily for the in vitro testing of antineoplastic agents.
A tumor necrosis factor receptor subtype that has specificity for TUMOR NECROSIS FACTOR ALPHA and LYMPHOTOXIN ALPHA. It is constitutively expressed in most tissues and is a key mediator of tumor necrosis factor signaling in the vast majority of cells. The activated receptor signals via a conserved death domain that associates with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.
A heterogeneous group of immunocompetent cells that mediate the cellular immune response by processing and presenting antigens to the T-cells. Traditional antigen-presenting cells include MACROPHAGES; DENDRITIC CELLS; LANGERHANS CELLS; and B-LYMPHOCYTES. FOLLICULAR DENDRITIC CELLS are not traditional antigen-presenting cells, but because they hold antigen on their cell surface in the form of IMMUNE COMPLEXES for B-cell recognition they are considered so by some authors.
Endogenous tissue constituents that have the ability to interact with AUTOANTIBODIES and cause an immune response.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
A type of connective tissue neoplasm typically arising from intralobular stroma of the breast. It is characterized by the rapid enlargement of an asymmetric firm mobile mass. Histologically, its leaf-like stromal clefts are lined by EPITHELIAL CELLS. Rare phyllodes tumor of the prostate is also known.
Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.
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.
The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes IMMUNE COMPLEX DISEASES.
The relationship between the dose of an administered drug and the response of the organism to the drug.
Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.
Antigens stimulating the formation of, or combining with heterophile antibodies. They are cross-reacting antigens found in phylogenetically unrelated species.
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.
Neoplasms of the brain and spinal cord derived from glial cells which vary from histologically benign forms to highly anaplastic and malignant tumors. Fibrillary astrocytomas are the most common type and may be classified in order of increasing malignancy (grades I through IV). In the first two decades of life, astrocytomas tend to originate in the cerebellar hemispheres; in adults, they most frequently arise in the cerebrum and frequently undergo malignant transformation. (From Devita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2013-7; Holland et al., Cancer Medicine, 3d ed, p1082)
Nuclear antigens encoded by VIRAL GENES found in HUMAN HERPESVIRUS 4. At least six nuclear antigens have been identified.
Infections produced by oncogenic viruses. The infections caused by DNA viruses are less numerous but more diverse than those caused by the RNA oncogenic viruses.
A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
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.
Transfer of a neoplasm from its primary site to lymph nodes or to distant parts of the body by way of the lymphatic system.
Tomography using x-ray transmission and a computer algorithm to reconstruct the image.
A tumor necrosis factor receptor subtype found in a variety of tissues and on activated LYMPHOCYTES. It has specificity for FAS LIGAND and plays a role in regulation of peripheral immune responses and APOPTOSIS. Multiple isoforms of the protein exist due to multiple ALTERNATIVE SPLICING. The activated receptor signals via a conserved death domain that associates with specific TNF RECEPTOR-ASSOCIATED FACTORS in the CYTOPLASM.
A group of differentiation surface antigens, among the first to be discovered on thymocytes and T-lymphocytes. Originally identified in the mouse, they are also found in other species including humans, and are expressed on brain neurons and other cells.
An albumin obtained from the white of eggs. It is a member of the serpin superfamily.
A class of immunoglobulin bearing mu chains (IMMUNOGLOBULIN MU-CHAINS). IgM can fix COMPLEMENT. The name comes from its high molecular weight and originally being called a macroglobulin.
Sialylated Lewis blood group carbohydrate antigen found in many adenocarcinomas of the digestive tract, especially pancreatic tumors.
Technique involving the diffusion of antigen or antibody through a semisolid medium, usually agar or agarose gel, with the result being a precipitin reaction.
Carbohydrate antigen most commonly seen in tumors of the ovary and occasionally seen in breast, kidney, and gastrointestinal tract tumors and normal tissue. CA 125 is clearly tumor-associated but not tumor-specific.
DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.
A costimulatory ligand expressed by ANTIGEN-PRESENTING CELLS that binds to CD28 ANTIGEN with high specificity and to CTLA-4 ANTIGEN with low specificity. The interaction of CD86 with CD28 ANTIGEN provides a stimulatory signal to T-LYMPHOCYTES, while its interaction with CTLA-4 ANTIGEN may play a role in inducing PERIPHERAL TOLERANCE.
A group of malignant tumors of the nervous system that feature primitive cells with elements of neuronal and/or glial differentiation. Use of this term is limited by some authors to central nervous system tumors and others include neoplasms of similar origin which arise extracranially (i.e., NEUROECTODERMAL TUMORS, PRIMITIVE, PERIPHERAL). This term is also occasionally used as a synonym for MEDULLOBLASTOMA. In general, these tumors arise in the first decade of life and tend to be highly malignant. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, p2059)
Tumors or cancer of the GASTROINTESTINAL TRACT, from the MOUTH to the ANAL CANAL.
The hepatitis B antigen within the core of the Dane particle, the infectious hepatitis virion.
A benign epithelial tumor with a glandular organization.
A blue-red, extremely painful vascular neoplasm involving a glomeriform arteriovenous anastomosis (glomus body), which may be found anywhere in the skin, most often in the distal portion of the fingers and toes, especially beneath the nail. It is composed of specialized pericytes (sometimes termed glomus cells), usually in single encapsulated nodular masses which may be several millimeters in diameter (From Stedman, 27th ed). CHEMODECTOMA, a tumor of NEURAL CREST origin, is also sometimes called a glomus tumor.
A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
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)
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.

A possible contributory role of BK virus infection in neuroblastoma development. (1/1118)

The tumor suppressor protein p53 is aberrantly localized to the cytoplasm of neuroblastoma cells, compromising the suppressor function of this protein. Such tumors are experimentally induced in transgenic mice expressing the large tumor (T) antigen of polyomaviruses. The oncogenic mechanisms of T antigen include complex formation with, and inactivation of, the tumor suppressor protein p53. Samples from 18 human neuroblastomas and five normal human adrenal glands were examined. BK virus DNA was detected in all neuroblastomas and none of five normal adrenal glands by PCR. Using DNA in situ hybridization, polyomaviral DNA was found in the tumor cells of 17 of 18 neuroblastomas, but in none of five adrenal medullas. Expression of the large T antigen was detected in the tumor cells of 16 of 18 neuroblastomas, but in none of the five adrenal medullas. By double immunostaining BK virus T antigen and p53 was colocalized to the cytoplasm of the tumor cells. Immunoprecipitation revealed binding between the two proteins. The presence and expression of BK virus in neuroblastomas, but not in normal adrenal medulla, and colocalization and binding to p53, suggest that this virus may play a contributory role in the development of this neoplasm.  (+info)

The retinoblastoma protein alters the phosphorylation state of polyomavirus large T antigen in murine cell extracts and inhibits polyomavirus origin DNA replication. (2/1118)

The retinoblastoma tumor suppressor protein (pRb) can associate with the transforming proteins of several DNA tumor viruses, including the large T antigen encoded by polyomavirus (Py T Ag). Although pRb function is critical for regulating progression from G1 to S phase, a role for pRb in S phase has not been demonstrated or excluded. To identify a potential effect of pRb on DNA replication, pRb protein was added to reaction mixtures containing Py T Ag, Py origin-containing DNA (Py ori-DNA), and murine FM3A cell extracts. We found that pRb strongly represses Py ori-DNA replication in vitro. Unexpectedly, however, this inhibition only partially depends on the interaction of pRb with Py T Ag, since a mutant Py T Ag (dl141) lacking the pRb interaction region was also significantly inhibited by pRb. This result suggests that pRb interferes with or alters one or more components of the murine cell replication extract. Furthermore, the ability of Py T Ag to be phosphorylated in such extracts is markedly reduced in the presence of pRb. Since cyclin-dependent kinase (CDK) phosphorylation of Py T Ag is required for its replication function, we hypothesize that pRb interferes with this phosphorylation event. Indeed, the S-phase CDK complex (cyclin A-CDK2), which phosphorylates both pRb and Py T Ag, alleviates inhibition caused by pRb. Moreover, hyperphosphorylated pRb is incapable of inhibiting replication of Py ori-DNA in vitro. We propose a new requirement for maintaining pRb phosphorylation in S phase, namely, to prevent deleterious effects on the cellular replication machinery.  (+info)

The simian virus 40 small-t and large-T antigens jointly regulate cell cycle reentry in human fibroblasts. (3/1118)

Focus formation in human diploid fibroblasts (HDF cells) is known to require both the simian virus 40 (SV40) large-T and small-t antigens. Similarly, both SV40 proteins were required to stimulate confluent, density-arrested HDF cells to reenter the cell cycle. This study used defective recombinant adenoviruses to examine the roles of the individual SV40 proteins in altering specific steps in the cell cycle. Small-t antigen and, to a lesser extent, large-T antigen increased the level of the S phase cyclin cyclin A but without increasing the activity of associated cyclin kinases unless the two SV40 proteins were coexpressed. The absence of kinase activity reflected the presence in density-arrested cells of high levels of the cyclin-dependent kinase inhibitors p21(WAF1) and p27(KIP1). We report here that expression of SV40 large-T antigen reduced levels of p21(WAF1), while expression of small-t antigen was required to decrease p27(KIP1). The separate effects of large-T and small-t antigens on these two inhibitors may explain the joint requirement for the two proteins to drive cell cycle reentry of HDF cells and ultimately transform these cells.  (+info)

The J domain of papovaviral large tumor antigen is required for synergistic interaction with the POU-domain protein Tst-1/Oct6/SCIP. (4/1118)

Large T antigens from polyomaviruses are multifunctional proteins with roles in transcriptional regulation, viral DNA replication, and cellular transformation. They have been shown to enhance the activity of various cellular transcription factors. In the case of the POU protein Tst-1/Oct6/SCIP, this enhancement involves a direct physical interaction between the POU domain of the transcription factor and the amino-terminal region of large T antigen. Here we have analyzed the structural requirements for synergistic interaction between the two proteins in greater detail. Tst-1/Oct6/SCIP and the related POU protein Brn-1 were both capable of direct physical interaction with large T antigen. Nevertheless, only Tst-1/Oct6/SCIP functioned synergistically with large T antigen. This differential behavior was due to differences in the amino-terminal regions of the proteins, as evident from chimeras between Tst-1/Oct6/SCIP and Brn-1. Synergy was specifically observed for constructs containing the amino-terminal region of Tst-1/Oct6/SCIP. Large T antigen, on the other hand, functioned synergistically with Tst-1/Oct6/SCIP only when the integrity of its J-domain-containing amino terminus was maintained. Mutations that disrupted the J domain concomitantly abolished the ability to enhance the function of Tst-1/Oct6/SCIP. The J domain of T antigen was also responsible for the physical interaction with Tst-1/Oct6/SCIP and could be replaced in this property by other J domains. Intriguingly, a heterologous J domain from a human DnaJ protein partially substituted for the amino terminus of T antigen even with regard to the synergistic enhancement of Tst-1/Oct6/SCIP function. Given the general role of J domains, we propose chaperone activity as the underlying mechanism for synergy between Tst-1/Oct6/SCIP and large T antigens.  (+info)

New insights into the mechanism of inhibition of p53 by simian virus 40 large T antigen. (5/1118)

Simian virus 40 (SV40) large tumor antigen (T antigen) has been shown to inhibit p53-dependent transcription by preventing p53 from binding to its cognate cis element. Data presented in this report provide the first direct functional evidence that T antigen, under certain conditions, may also repress p53-dependent transcription by a mechanism in which the transactivation domain of p53 is abrogated while DNA binding is unaffected. Specifically, p53 purified as a complex with T antigen from mouse cells was found to bind DNA as a transcriptionally inactive intact complex, while that purified from human cells was found to bind DNA independently of T antigen and could activate p53-dependent transcription. This difference in activity may be dependent on a different interaction of T antigen with mouse and human p53 and, in addition, on the presence of super T, which is found only in transformed rodent cells. These results suggest that subtle yet important differences exist between the inhibition of p53 by T antigen in mouse and human cells. The implications of this finding with respect to SV40-associated malignancies are discussed.  (+info)

A kinase activity associated with simian virus 40 large T antigen phosphorylates upstream binding factor (UBF) and promotes formation of a stable initiation complex between UBF and SL1. (6/1118)

Simian virus 40 large T antigen is a multifunctional protein which has been shown to modulate the expression of genes transcribed by RNA polymerase I (Pol I), II, and III. In all three transcription systems, a key step in the activation process is the recruitment of large T antigen to the promoter by direct protein-protein interaction with the TATA binding protein (TBP)-TAF complexes, namely, SL1, TFIID, and TFIIIB. However, our previous studies on large T antigen stimulation of Pol I transcription also revealed that the binding to the TBP-TAFI complex SL1 is not sufficient to activate transcription. To further define the molecular mechanism involved in large T antigen-mediated Pol I activation, we examined whether the high-mobility group box-containing upstream binding factor (UBF) plays any role in this process. Here, using cell labeling experiments, we showed that large T antigen expression induces an increase in UBF phosphorylation. Further biochemical analysis demonstrated that UBF is phosphorylated by a kinase activity that is strongly associated with large T antigen, and that the carboxy-terminal activation domain of UBF is required for the phosphorylation to occur. Using in vitro reconstituted transcription assays, we demonstrated that the inability of alkaline phosphatase treated UBF to efficiently activate transcription can be rescued by large T antigen. Moreover, we showed that large T antigen-induced UBF phosphorylation promotes the formation of a stable UBF-SL1 complex. Together, these results provide strong evidence for an important role for the large T antigen-associated kinase in mediating the stimulation of RNA Pol I transcription.  (+info)

Atm is dispensable for p53 apoptosis and tumor suppression triggered by cell cycle dysfunction. (7/1118)

Both p53 and ATM are checkpoint regulators with roles in genetic stabilization and cancer susceptibility. ATM appears to function in the same DNA damage checkpoint pathway as p53. However, ATM's role in p53-dependent apoptosis and tumor suppression in response to cell cycle dysregulation is unknown. In this study, we tested the role of murine ataxia telangiectasia protein (Atm) in a transgenic mouse brain tumor model in which p53-mediated apoptosis results in tumor suppression. These p53-mediated activities are induced by tissue-specific inactivation of pRb family proteins by a truncated simian virus 40 large T antigen in brain epithelium. We show that p53-dependent apoptosis, transactivation, and tumor suppression are unaffected by Atm deficiency, suggesting that signaling in the DNA damage pathway is distinct from that in the oncogene-induced pathway. In addition, we show that Atm deficiency has no overall effect on tumor growth and progression in this model.  (+info)

Telomerase extends the lifespan of virus-transformed human cells without net telomere lengthening. (8/1118)

Human fibroblasts whose lifespan in culture has been extended by expression of a viral oncogene eventually undergo a growth crisis marked by failure to proliferate. It has been proposed that telomere shortening in these cells is the property that limits their proliferation. Here we report that ectopic expression of the wild-type reverse transcriptase protein (hTERT) of human telomerase averts crisis, at the same time reducing the frequency of dicentric and abnormal chromosomes. Surprisingly, as the resulting immortalized cells containing active telomerase continue to proliferate, their telomeres continue to shorten to mean lengths below those in control cells that enter crisis. These results provide evidence for a protective function of human telomerase that allows cell proliferation without requiring net lengthening of telomeres.  (+info)

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Return to Modified Bases Modifications Super T (5-hydroxybutynl-2-deoxyuridine) is a duplex-stabilizing modified base that increases oligonucleotide Tm. Oligonucleotides containing Super T can be extended normally by polymerases, including Taq polymerase,making Super T a useful modified base for designing short primers or probes for low-complexity, A-T rich sequences. ...
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Abstract: Abstract Polyomaviruses have provided many insights into control of cell physiology. Studies of their tumor antigens (Tags) have led to appreciation of the role of tyrosine phosphorylation, PI3K and p53 in oncogenic transformation. This work explores signal pathways regulated by polyomavirus small T antigen (PyST) that control differentiation and regulate cell survival in fat, muscle and... read more bone models. Comparisons of murine polyomavirus ST (PyST) to monkey polyomavirus SV40 (SV40 ST) have been especially useful in parsing out the mechanisms involved. This work also makes use of PyST mutants defective in specific interactions. Of the many PyST functions, we particularly illustrate the importance of phosphatase 2A (PP2A) for PyST to regulate differentiation. PP2A regulates almost all cell signaling pathways. The holoenzyme consists of a catalytic C subunit and one of many regulatory B subunits bound to an A scaffolding subunit. Of more than 80 PP2A isoforms, 10% use Abeta as a ...
The oligomers formed by a mutant nonkaryophilic large T antigen of simian virus 40, which lacks residues 110 through 152 of normal large T antigen and transforms only established cells (L. Fischer-Fantuzzi and C. Vesco, Proc. Natl. Acad. Sci. USA 82:1891-1895, 1985), were found to consist predominantly of dimers. Anti-p53 antibodies precipitated 14 to 16S complexes containing the mutant nonkaryophilic large T antigen and p53 from extracts of transformed cells, and anti-p53 indirect immunofluorescence stained these cells in the cytoplasm. ...
Buy our Recombinant Simian Virus 40 (SV40) SV40 Large T Antigen protein. Ab82118 is a full length protein produced in Baculovirus and has been validated in…
Deppert, W and Walter, G, Domains of simian virus 40 large t-antigen exposed on the cell surface. (1982). Subject Strain Bibliography 1982. 3601 ...
Cells were derived by infection of hTERT-HPNE E6/E7 cells (ATCC CRL-4036) with retroviral vector (pBabeZeo) carrying the SV40 small t antigen
Cancers that display a specific combination of sugars, called T-antigen, are more likely to spread through the body and kill a patient. However, what regulates the appearance of T-antigen in cancer cells, the set of proteins modified with T-antigen, and the roles the T-antigen and the modified proteins play during metastasis, is not yet understood.
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This entry was posted on June 2, 2011, 3:42 am and is filed under Fugitive Document. You can follow any responses to this entry through RSS 2.0. You can leave a response, or trackback from your own site. ...
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generating the core 1 O-glycan Gal-beta1-3GalNAc-alpha1-Ser/Thr (T antigen), which is a precursor for many extended O-glycans in ...
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The simian virus 40 small T-associated 56,000-Mr (56K) and 32K cellular proteins were shown to be closely related to the polyomavirus medium T-associated 61K and 37K cellular proteins as demonstrated by two-dimensional polyacrylamide gel electrophoresis and V8 protease peptide mapping. ...
Simian virus (SV40) large T antigen, molecular model. This antigen is from the simian vacuolating virus 40 (SV40). Large T antigens play a role in regulating the viral life cycle of the polyomaviridae viruses, such as SV40. SV40 is found in monkeys such as Rhesus monkeys and macaques. Potentially tumour-causing in primates and humans, it is used in laboratory research and in vaccines. - Stock Image C025/1808
Looking for online definition of T-antigen in the Medical Dictionary? T-antigen explanation free. What is T-antigen? Meaning of T-antigen medical term. What does T-antigen mean?
TY - JOUR. T1 - Further characterisation of the complex containing middle T antigen and pp60.. AU - Courtneidge, Sara. PY - 1989. Y1 - 1989. UR - UR - M3 - Article. C2 - 2477198. AN - SCOPUS:0024387934. VL - 144. SP - 121. EP - 128. JO - Current Topics in Microbiology and Immunology. JF - Current Topics in Microbiology and Immunology. SN - 0070-217X. ER - ...
This topic contains 11 study abstracts on Simian virus 40 (SV40) indicating it may contribute to Simian virus 40 (SV40), Mesothelioma, and Cancer Metastasis
You searched for: Creator Nathans, Daniel, 1928-1999 Remove constraint Creator: Nathans, Daniel, 1928-1999 Creator Lee, Theresa N. H. (Theresa N. H. Lee) Remove constraint Creator: Lee, Theresa N. H. (Theresa N. H. Lee) Subject DNA Cleavage Remove constraint Subject: DNA Cleavage Subject Simian virus 40 Remove constraint Subject: Simian virus 40 ...
Kupffer cells have been isolated from transgenic mice carrying a thermolabile SV40 large tumor antigen under the H2Kb promoter (kind gift of D. Kioussis, NIMR, London). The cells grow with Interferon-gamma at 33oC, at which temperature the promoter is turned on and the SV40T Ag is active. They differentiate at 39oC. These cells are now being characterised: cytokine and NO liberation is stimulated, surface receptors are assessed at the mRNA and protein level, and phagocytosis and uptake of bacterial components are being measured. Results will be compared with the functional characteristics of primary Kupffer cells isolated from normal mice (see also 3R project 73-00) Conclusions and Relevance for 3R ...
Nuclear targeting sequences are essential for the transport of proteins into the nucleus. The seven-amino-acid nuclear targeting sequence of the SV40 large T antigen has been regarded as the model; however, many nuclear targeting sequences appear to be more complex. We suggest in this review that, d …
The basic nature of viral selectivity for certain species, certain organs, certain cells, and certain sites within these cells constitutes a broad and deep problem that penetrates to the level of the ...
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Molecular Oncology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA. Signal transducers and activators of transcription (STATs) were originally identified as key components of signaling pathways involved in mediating responses to IFNs. Previous studies showed that the Src oncoprotein constitutively activates one STAT family member, Stat3. In this study, we investigated STAT activation in a panel of rodent fibroblast cell lines stably transformed by diverse viral oncoproteins. Using a temperature-sensitive mutant of v-Src, we determined that Stat3 is activated within 15 min of shift from nonpermissive to permissive temperature for cell transformation. This finding indicates that v-Src tyrosine kinase activity is required for Stat3 activation and suggests that Stat3 is proximal to signaling initiated by Src. In addition, Stat3 activation is induced by another nonreceptor tyrosine kinase, v-Fps; by polyoma virus middle T antigen, which activates Src family kinases; ...
DELETION OF THE CARBOXY TERMINUS OT SIMIAN VIRUS 40 LARGE T ANTIGEN AFFECTS VIRAL LATE GENE EXPRESSION A Thesis Submitted to the Faculty in partial fulfillment of the requirements for the degree of Doctor of Philosophy Terryl Stacy DARTMOUTH COLLEGE Hanover, New Hampshire March 8,1990 ...
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Zdroj: Immunol Lett. 2020 Mar;219:46-53. doi: 10.1016/j.imlet.2020.01.001. Epub 2020 Jan 10. Authors: O. Palata, N. Podzimkova Hradilova, D. Mysiková, B. Kutna, H. Mrazkova, R. Lischke, R. Spisek, I. Adkins. ...
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We used to take Dover to one, but he HATED the staff there. Terrified of every last one of them, one in particular. He was so terrified that he would urinate every time one of them walked in the door. They made me leave him there once, for an exam, and refused to let me stay with him even though all it was were shots and a fecal. I could never understand why, and hes been terrified ever since. The only possibilities I have come up with in my mind are abuse of some sort, from someone on the staff or less than ideal treatment, so I paid the rest of his insurance, and left. He is not afraid of anyone else, not a single person, except the doctors and staff of that particular hospital. Definitely not a Banfield thing, it was THIS hospital, with THIS staff ...
TY - JOUR. T1 - Simian virus 40 large T antigen (SV40LTAg) primer specific DNA amplification in human pleural mesothelioma tissue. AU - Pepper, Christopher. AU - Jasani, Bharat. AU - Navabi, Hossein. AU - Wynford-Thomas, David. AU - Gibbs, Allen R.. N1 - Copyright: Copyright 2017 Elsevier B.V., All rights reserved.. PY - 1996. Y1 - 1996. N2 - Background - DNA sequences and immunoreactivity associated with Simian virus 40 transforming factors, large T and small T antigens (SV40LTAg), suggestive of an aetiopathogenetic link have been identified in fresh frozen tissue of a high proportion of recent cases of pleural mesotheliomas from the United States, Italy and Germany. SV40 is not normally infective in human though it can transform human cells in tissue culture. A large cohort of people in the western world was accidentally parenterally inoculated with live SV40 through contaminated polio vaccines given between 1959 and 1961, and this might be a factor in the current continuing rise in the ...
Looking for online definition of renal tumour antigen in the Medical Dictionary? renal tumour antigen explanation free. What is renal tumour antigen? Meaning of renal tumour antigen medical term. What does renal tumour antigen mean?
Antisera prepared in syngeneic mice by hyperimmunization with intact SV40-transformed mouse cells or with somatic cell hybrids between SV40-transformed human and normal mouse cells exhibit anti-SV40 tumor (T) antigen reactivity. Athymic mice bearing tumors formed by SV40-transformed mouse, human or mouse-human hybrids were not reactive with SV40 T antigen. Anti-thymocyte serum (ATS)-treated mice also lacked T antigen reactivity during suppressive treatment but developed antibody to T antigen after discontinuing ATS treatment and tumor regression. We conclude that that presence of growing tumors in the mouse is not necessary for the production of anti-SV40 T antigen antibodies but that helper thymus-derived cells are essential for the humoral response.
Much has been learned in recent years concerning the nature of tumor antigens recognized by T cells. To apply this knowledge clinically, the nature of the host response to individual and multiple tumor antigens has to be characterized. This will help to define the efficacy of immune surveillance and the immune status of the host following exposure to tumor antigens expressed on pre-neoplastic tissue. To approach these questions, we have developed a transgenic mouse which expresses the tumor-specific antigen P91A. The single amino acid substitution in P91A results in the expression of a new MHC class I (H-2Ld)-binding peptide. In transgenic tissue, the H-2Ld/P91A complex is expressed in isolation from other tumor-associated antigens, allowing definition of the immune response to a single defined tumor antigen, a situation closely analogous to events during tumorigenesis. We show that CD8+ T cell immune surveillance of P91A is ineffective without the introduction of a helper determinant operating ...
Cerebral cortical development requires orderly transitions between neurogenesis and differentiation. Neurogenesis also results in overproduction of neurons that are selectively targeted for apoptosis. In these experiments, we conditionally immortalized (Almazan and McKay, 1992; Yanai and Obinata, 1994; Taher et al., 1995; Eves et al., 1996) neural precursors from embryonic rat cerebral cortex, to contrast estrogen and neurotrophin regulation of p53-dependent cortical differentiation and death.. The large T antigen promotes mammalian cell cycle by inhibiting checkpoint transcription factors like p53 (for review, see Levine, 1997). Consequently, the Ts/U19 large T antigen mutation permits synchronization of differentiation, by conditionally regulating p53-dependent mechanisms. At the nonpermissive temperature (39°C), large T antigen expression ceases and substantial cell death occurs, that is partly caused by apoptosis. At this temperature, we also observed induction of pp53 and p53-dependent ...
TY - JOUR. T1 - Immortalization of subpopulations of respiratory epithelial cells from transgenic mice bearing SV40 large T antigen. AU - Ikeda, K.. AU - Clark, J. C.. AU - Bachurski, C. J.. AU - Wikenheiser, K. A.. AU - Cuppoletti, J.. AU - Mohanti, S.. AU - Morris, R. E.. AU - Whitsett, J. A.. PY - 1994. Y1 - 1994. UR - UR - M3 - Article. AN - SCOPUS:0028041963. VL - 267. JO - American Journal of Physiology - Heart and Circulatory Physiology. JF - American Journal of Physiology - Heart and Circulatory Physiology. SN - 0363-6135. IS - 3 part 1. ER - ...
Abstract Background The mammary glands of pigs share many functional and morphological similarities with the breasts of humans, raising the potential of their utility for research into the mechanisms underlying normal mammary function and breast carcinogenesis. Here we sought to establish a model for the efficient manipulation and transformation of porcine mammary epithelial cells (pMEC) in vitro and tumor growth in vivo. Methods We utilized a vector encoding the red florescent protein tdTomato to transduce populations of pMEC from Yorkshire -Hampshire crossbred female pigs in vitro and in vivo. Populations of primary pMEC were then separated by FACS using markers to distinguish epithelial cells (CD140a-) from stromal cells (CD140a+), with or without further enrichment for basal and luminal progenitor cells (CD49f+). These separated pMEC populations were transduced by lentivirus encoding murine polyomavirus T antigens (Tag) and tdTomato and engrafted to orthotopic or ectopic sites in ...
Janelle, Valérie; Lamarre, Alain (2014). How Informative is the Immune Response Against Surrogate Tumor Antigens to Assess Antitumor Immunity? Frontiers in oncology , vol. 4 , nº 135. p. 1-3. DOI: 10.3389/fonc.2014.00135. ...
p53 is a cellular-encoded phosphoprotein first identified in protein complexes with the large tumor (T) antigen of simian virus 40 (SV40) (Linzer and Levine, 1979; Lane and Crawford, 1979). High...
4FGN: Analysis of the Costructure of the Simian Virus 40 T-Antigen Origin Binding Domain with Site I Reveals a Correlation between GAGGC Spacing and Spiral Assembly.
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This enhances the anti-tumor immune response to tumor antigens released following viral lysis and provides a patient-specific ... shared tumor antigens; and unique tumor antigens. Shared antigens are expressed by many tumors. Unique tumor antigens result ... Escape loss variants (that target a single tumor antigen are likely to be less effective. Tumors are heterogeneous and antigen ... Antigen candidates[edit]. Tumor antigens have been divided into two categories: ...
It was seen in this study that p53 could bind to viral tumor antigens. This information was corroborated during the same year ... which causes antigen-presenting cells to present tumor antigens, resulting in an immune response against tumors. It has also ... J Virol 69:5422-5430 Nuesch JP, Bar S, Rommelaere J (2008) Viral proteins killing tumor cells: new weapons in the fight against ... It was seen in one Phase I clinical trial that injecting mda-7 via an adenovirus directly into a tumor resulted in safe tumor ...
They could therefore be used to vaccinate against viral, bacterial, protozoan, and tumor antigens. Initially, the Togaviridae ... The proteolytic maturation of P62 into E2 and E3 causes a change in the viral surface. Together the E1, E2, and sometimes E3, ... Larger mammals such as humans and horses are usually dead-end hosts or play a minor role in viral transmission; however, in the ... The viral membrane-anchored surface glycoproteins are responsible for receptor recognition and entry into target cells through ...
Transplantation antigens and their changes in carcinogenesis and viral infection. In: Virusnyi onkoliz i iskusstvennaya ... Viral Oncolysis and Artificial Heterogenization of Tumors). Riga, pp. 217-234. the stem bark of Mappia foetida, a tree native ... According to the Ebers medical papyrus, this was done by placing a poultice near the tumour, followed by local incision. BC - ... According to Littrup et al., who performed cryoablation of breast tumors in clinical stages I-IV with a multi-probe freeze ...
This process is necessary for immunity against most tumors and viruses that do not readily infect antigen-presenting cells, but ... Also, cross-priming avoids viral immune evasion strategies, such as suppression of antigen processing. Consequently, immune ... This mass generation of activated tumor specific CD8+ T cells increases anti-tumor immunity, and is also able to overcome many ... Cross-presentation is the ability of certain antigen-presenting cells to take up, process and present extracellular antigens ...
MHC class I molecules are the main mechanism by which cells display viral or tumor antigens to cytotoxic T cells. A common ... Tumor cell surveillance[edit]. Natural killer cells often lack antigen-specific cell surface receptors, so are part of innate ... They serve to contain viral infections while the adaptive immune response generates antigen-specific cytotoxic T cells that can ... Instead of acting via antigen-specific receptors, lysis of tumor cells by NK cells is mediated by alternative receptors, ...
MHC class I molecules are the main mechanism by which cells display viral or tumor antigens to cytotoxic T cells. A common ... Instead of acting via antigen-specific receptors, lysis of tumor cells by NK cells is mediated by alternative receptors, ... They serve to contain viral infections while the adaptive immune response generates antigen-specific cytotoxic T cells that can ... Tumor cell detection results in activation of NK cells and consequent cytokine production and release. If tumor cells do not ...
This antigen possesses tumor epitopes capable of inducing HLA-A24-restricted and tumor-specific cytotoxic T lymphocytes in ... This gene product is found to be an important cellular factor for HIV-1 gene expression and viral replication. It also ... Harada K, Yamada A, Yang D, Itoh K, Shichijo S (September 2001). "Binding of a SART3 tumor-rejection antigen to a pre-mRNA ... The protein encoded by this gene is an RNA-binding nuclear protein that is a tumor-rejection antigen. ...
Ramqvist, T; Dalianis, T (August 2009). "Murine polyomavirus tumour specific transplantation antigens and viral persistence in ... these proteins are expressed from the early region of the viral genome and are known as large, middle, and small tumor antigen ... and small tumor antigens (LT, MT, ST) and are sufficient for inducing tumors. The three genes in the late region express the ... In 2015 the genome sequence of a rat polyomavirus was reported to contain middle tumor antigen as well, consistent with ...
Ramqvist T, Dalianis T (August 2009). "Murine polyomavirus tumour specific transplantation antigens and viral persistence in ... All of the capsid proteins are expressed from the late region of the viral genome, so named because expression occurs only late ... Major capsid protein VP1 is a viral protein that is the main component of the polyomavirus capsid. VP1 monomers are generally ... The VP1 protein, along with capsid components VP2 and VP3, is expressed from the "late region" of the circular viral genome. ...
September 2009). "Detection of human herpesvirus-6 variants in pediatric brain tumors: association of viral antigen in low ... Because the tumor grade is based upon the most malignant portion of the tumor, biopsy or subtotal tumor resection can result in ... Imaging of tumor blood flow using perfusion MRI and measuring tumor metabolite concentration with MR spectroscopy may add ... The new 2016 WHO Classification of Tumors of the Central Nervous System was a paradigm shift: some of the tumors were defined ...
Lathe, Richard (1 December 1990). "Vaccination against tumor cells expressing breast cancer epithelial tumor antigen". ... Lafon, M. (2016). Reiss, Carol Shoshkes (ed.). Neurotropic Viral Infections (Vol. 1): Neurotropic RNA Viruses (2nd edn). https ... Extension of this work included the development of vaccines against virus-induced tumors. The European rabies vaccination ... Lathe, Richard (30 April 1987). "Tumour prevention and rejection with recombinant vaccinia". Nature. 326 (6116): 878-880. doi: ...
A suitable tumour-specific promoter for prostate cancer is prostate-specific antigen (PSA), whose expression is greatly ... CN706 is a CRAd with a PSA tumour-specific promoter driving expression of the adenoviral E1A gene, required for viral ... Phase I of the trial recruited patients with metastatic solid tumors and showed evidence for virus replication within tumour ... viral spread, tumour necrosis and anti-tumoural immune responses (see the EU Clinical Trials Register for further details). ...
Role of bone marrow-derived cells in presenting MHC class I-restricted tumor antigens. Science. 1994, 264 (5161): 961-5. PMID ... Cross-presentation in viral immunity and self-tolerance. Nat Rev Immunol. 2001, 1 (2): 126-34. PMID 11905820. doi:10.1038/ ... 當Michael J. Bevan注射了攜帶有次要組織相容性抗原(英语:Minor histocompatibility antigen)的移植細胞後,交叉呈現的證據於1976年被發現。他發現接受者的抗原呈現細胞誘導了CD8+毒殺T細胞對抗外來MHC細
Normal body cells are not recognized and attacked by NK cells because they express intact self MHC antigens. Those MHC antigens ... The NK-92 cell line does not express KIR and is developed for tumor therapy.[9][10][11][12] ... When host cells die, either by programmed cell death (also called apoptosis) or by cell injury due to a bacterial or viral ... Dendritic cells are very important in the process of antigen presentation, and serve as a link between the innate and adaptive ...
Attenuation involves deleting viral genes, or gene regions, to eliminate viral functions that are expendable in tumour cells, ... has been genetically engineered to replicate preferentially within tumor cells and to generate antigens that elicit an immune ... Transductional targeting involves modifying the viral coat proteins to target tumour cells while reducing entry to non-tumour ... Viruses selectively infect tumor cells because of their defective anti-viral response. Imlygic, an attenuated herpes simplex ...
Shark single domain antibodies (VNARs) to tumor or viral antigens can be isolated from a large naïve nurse shark VNAR library ... The resulting antibodies are designated IgW (also called IgX or IgNARC) and IgNAR (immunoglobulin new antigen receptor). The ... antigen interaction surface instead of the more familiar bivalent tip surface. The bovine CDR is unusually long and contains ... that is important for binding antigen and several constant domains (CH1, CH2, etc.). Production of a viable heavy chain is a ...
... the small tumor antigen, large tumor antigen, and alternative tumor antigen (ALTO); and three viral coat proteins, VP1, VP2, ... which canonically encodes the small and large tumor antigens; expression of ALTO has also been reported in trichodysplasia ... After doctors were unable to identify known viral causes of the patient's symptoms, a research team led by virologist Ian ... "Characterization of T Antigens, Including Middle T and Alternative T, Expressed by the Human Polyomavirus Associated with ...
... containing a small and large tumor antigen and three viral capsid proteins; it has no open reading frame corresponding to an ... prevalence of detectable antibodies against viral proteins indicating either past or present exposure - vary widely. A 2013 ...
Besides, an antigen can represent a bacterium, a virus or an allergen or a tumour cell. The high degree of complexity of the ... viral infections, hypersensitivity, etc. Since the first release of C-ImmSim, the code has been modified many times. The actual ... Computational modelling of the immune response to tumour antigens: implications for vaccination. J Theo Biol, 237(4):390-400 ( ... clonal selection by antigen affinity, thymic education of T cells, antigen processing and presentation (both the cytosolic and ...
"SV40 association with human malignancies and mechanisms of tumor immunity by large tumor antigen". Cellular and Molecular Life ... Initiation Signals in Viral Gene Expression pp 5-24 Chapter: Regulation of Viral Transcription and DNA Replication by the SV40 ... En ratas, o antíxeno T grande de SV40 oncoxénico foi utilizado para establecer un modelo de tumor cerebral para o tumor ... "A model for primitive neuroectodermal tumors in transgenic neural transplants harboring the SV40 large T antigen". The American ...
... viral, and tumor antigens". Blood. 107 (1): 151-8. doi:10.1182/blood-2005-03-1112. PMID 16166594. Mantovani A, Garlanda C, ... Lee GW, Lee TH, Vilcek J (March 1993). "TSG-14, a tumor necrosis factor- and IL-1-inducible protein, is a novel member of the ... Klouche M, Brockmeyer N, Knabbe C, Rose-John S (May 2002). "Human herpesvirus 8-derived viral IL-6 induces PTX3 expression in ... Lee TH, Wisniewski HG, Vilcek J (January 1992). "A novel secretory tumor necrosis factor-inducible protein (TSG-6) is a member ...
In tumors, the viral DNA has broken and become integrated into human DNA within the tumor, so that the virus is no longer ... Antibodies have been developed to stain for T antigen in tumor tissues and appear to be specific for MCV-infected tumor cells. ... and viral capsid proteins VP1 and VP2/3 genes (from late strand) [1]. MCV T antigen has similar features to the T antigens of ... The viral T antigen has truncation mutations that leave the T antigen unable to initiate DNA replication needed to propagate ...
One way to induce immortality is through viral-mediated induction of the large T‑antigen, commonly introduced through simian ... Immortal cell lines of cancer cells can be created by induction of oncogenes or loss of tumor suppressor genes. ...
At around 5.3 kilobase pairs in length, it contains genes for the small, middle, and large tumor antigens and three viral coat ... However, middle tumor antigen has also recently been reported in at least one virus of unrelated lineage, the trichodysplasia ... In 2015 the genome sequence of a rat polyomavirus was reported to contain middle tumor antigen as well, consistent with ... This observation is in contrast to the skin tumors, which carry substantial viral loads. The capacity to induce hematopoietic ...
... the large tumor antigen and small tumor antigen. The prevalence of KI virus as detected by the presence of its DNA in human ... encoding five viral proteins: three capsid components, major capsid protein VP1, VP2, and VP3; and two additional proteins ...
... the large tumor antigen and small tumor antigen. Although WU virus has been detected in a variety of locations around the world ... encoding five viral proteins: three capsid components, major capsid protein VP1, VP2, and VP3; and two additional proteins ...
These cells are then either pulsed with an antigen or tumor lysate or transfected with a viral vector, causing them to display ... March 2005). "CD8+ T cell immunity against a tumor/self-antigen is augmented by CD4+ T helper cells and hindered by naturally ... The extraction of G-CSF lymphocytes from the blood and expanding in vitro against a tumour antigen before reinjecting the cells ... The cells then destroy the tumor cells that express the antigen.[citation needed]Topical immunotherapy utilizes an immune ...
... state expressing the viral latency-associated nuclear antigen, LANA. Crucial for the Entry of the KSHV [10] is the EPH receptor ... While no other human tumor virus possesses these same genes, other tumor viruses target the same cellular pathways illustrating ... The viral episome is chromatinized upon entry into the host cell nucleus.[15] LANA tethers the viral DNA to cellular ... The viral genome consists of a ~145 kbase long unique region, encoding all of expressed viral genes, which is flanked by ~20-30 ...
Interleukin-10 determines viral clearance or persistence in vivo. Nature Medicine. November 2006, 12 (11): 1301-9. PMC 2535582 ... T Cells to protect tumour cells. Nature Communications. March 2018, 9 (1): 948. PMC 5838096. PMID 29507342. doi:10.1038/s41467- ... MR1 antigen presentation to mucosal-associated invariant T cells was highly conserved in evolution. Proceedings of the National ... An induced rebinding model of antigen discrimination. Trends Immunol. 2014, 35 (4): 153-8. PMC 3989030. PMID 24636916. doi: ...
Tumor lysis syndrome, causing acute renal failure. *Infections *Hepatitis B reactivation. *Other viral infections ... It increases MHC II and adhesion molecules LFA-1 and LFA-3 (lymphocyte function-associated antigen). ... govo-" (ovarian tumor). Abagovomab. Igovomab. Oregovomab. "-pro-" (prostate tumor). Capromab pendetide. "-colo-" (colonic tumor ...
Graft-versus-tumor effect[edit]. Main article: Graft-versus-tumor effect. Graft-versus-tumor effect (GVT) or "graft versus ... for human leukocyte antigen (HLA) matching (see PGD for HLA matching) in order to donate to an ill sibling requiring HSCT. ... "A systematic review of viral infections associated with oral involvement in cancer patients: a spotlight on Herpesviridea" ... a b Memorial Sloan-Kettering Cancer Center , Blood & Marrow Stem Cell Transplantation , The Graft-versus-Tumor Effect Archived ...
Tumor lysis syndrome, causing acute renal failure. *Infections *Hepatitis B reactivation. *Other viral infections ... It increases MHC II and adhesion molecules LFA-1 and LFA-3 (lymphocyte function-associated antigen). ...
"Tissue Antigens. 64 (5): 575-80. doi:10.1111/j.1399-0039.2004.00310.x. PMID 15496200.. ... Most important of which is the TNF (tumor necrosis factors) with 3 loci in the region. Starting from B8, immediately followed ... or alternatively the result of chronic viral infection which is known to also elevate anti-tranglutaminase antibody. A German ... An A1::DQ2 appears in India, however its major antigen genes superficially resemble European A1-B8 and it appears to be a ...
... , also known as Lassa hemorrhagic fever (LHF), is a type of viral hemorrhagic fever caused by the Lassa virus.[1] ... However, immunofluorescence essays provide less definitive proof of Lassa infection.[7] An ELISA test for antigen and ... Viral Hemorrhagic Fever Consortium Lassa fever Archived 4 April 2015 at the Wayback Machine. Page accessed April 6, 2016 ... Clinically, Lassa fever infections are difficult to distinguish from other viral hemorrhagic fevers such as Ebola and Marburg ...
tumors, frequently solid tumors of the lung and colon; hematological malignancies such as chronic lymphocytic leukemia are less ... The immune complexes are formed by binding of antibodies to antigens in the glomerular basement membrane. The antigens may be ... Within membranous glomerulonephritis, especially in cases caused by viral hepatitis, serum C3 levels are low.[7] ... Other studies have implicated neutral endopeptidase and cationic bovine serum albumin as antigens.[4] ...
A map of the genome of JC virus, indicating the position of the tumor antigen genes (red), the three capsid protein genes ( ... T-antigen, also plays a key role in viral proliferation,[11] directing the initiation of DNA replication for the virus as well ... The Spi-B factor was shown to be crucial in initiating viral replication in certain strains of transgenic mice.[10] The protein ... Further research is needed to determine the exact etiological role of T-antigen, but there seems to be a connection to the ...
... viral burden - viral core - viral culture - viral envelope - viral load - viremia - viricide - virion - virology - virus - ... antigen - antigen presentation - antigen-presenting cell (APC) - antineoplastic - antiprotozoal - antiretroviral drugs - ... tumor necrosis factor (TNF) ... human leukocyte antigens (HLA) - human papilloma virus (HPV) - ...
These cells bind antigens presented on MHC I complex of virus-infected or tumour cells and kill them. Nearly all nucleated ... Infectious diseases - viral (AIDS, SARS, West Nile encephalitis, hepatitis, herpes, measles, others), bacterial (TB, typhoid, ... CD8+ cytotoxic T cells: virus-infected and tumor cells.. *γδ T cells: bridge between innate and adaptive immune responses; ... Natural killer cells: virus-infected and tumor cells.. Deeply staining, eccentric. NK-cells and cytotoxic (CD8+) T-cells. Years ...
... have been produced primarily by ex-vivo cultures and by the expansion of T-lymphocytes after stimulation with viral antigens. ... Immune deficiencies can result in persistent or recurring infections, autoinflammatory disorders, tumors, and disorders of ... This is carried out by using donor-derived antigen-presenting cells. These new methods have reduced culture time to 10-12 days ... It is a treatment that has been effective in preventing and treating viral infections after HSCT. VST therapy uses active donor ...
Group-specific antigen (gag) proteins are major components of the viral capsid, which are about 2000-4000 copies per virion. ... Retroviruses that cause tumor growth include Rous sarcoma virus and Mouse mammary tumor virus. Cancer can be triggered by proto ... The host cell then treats the viral DNA as part of its own genome, transcribing and translating the viral genes along with the ... This step will also make viral enzymes and capsid proteins (8). Viral RNA will be made in the nucleus. These pieces are then ...
Yersin looked for the germ responsible for the infection specifically in these plague-spots, tumors caused by the inflammation ... as an antigen, Richard F. J. Pfeiffer introduced it in the abdomen of a guinea pig already vaccinated against this disease, and ... serum which was able to agglutinate the bacteria and neutralize the toxin was supplied by a horse inoculated with the viral ... and they deduced that it can play the role of antigen, that is if they could overcome the delicate moment of its injection, ...
rid the body of neutralized antigen-antibody complexes.. Elements of the complement cascade can be found in many non-mammalian ... Instead, NK cells destroy compromised host cells, such as tumor cells or virus-infected cells. It recognises such cells by a ... This can occur in viral infections of host cells.[8] They were named "natural killer" because they do not require activation in ... Activates the adaptive immune system through a process known as antigen presentation. ...
... carcinoembryonic antigen, and mucins may aid in diagnosis.[45] Most tumors (,90%) are adenocarcinomas.[46] ... whether in the form of viral hepatitis (e.g. hepatitis B or hepatitis C),[22][23][24] alcoholic liver disease, or cirrhosis of ... However, if the tumor tissue margins are positive, indicating that the tumor was not completely removed via surgery, then ... For surgical cases, the odds of cure vary depending on the tumor location and whether the tumor can be completely, or only ...
Viral antigens[edit]. For virus-associated tumors, such as cervical cancer and a subset of head and neck cancers, epitopes ... Tumor antigens[edit]. Tumor antigens are those antigens that are presented by MHC class I or MHC class II molecules on the ... Antigens found only on such cells are called tumor-specific antigens (TSAs) and generally result from a tumor-specific mutation ... More common are antigens that are presented by tumor cells and normal cells, called tumor-associated antigens (TAAs). Cytotoxic ...
negative regulation of viral genome replication. • humoral immune response. • positive regulation of interleukin-8 production. ... "Cytotoxicity mediated by soluble antigen and lymphocytes in delayed hypersensitivity. 3. Analysis of mechanism". J. Exp. Med ... TNF, DIF, TNF-alpha, TNFA, TNFSF2, Tumour necrosis factor, TNF-α, tumor necrosis factor, TNLG1F, Tumor necrosis factor alpha. ... Tumor necrosis factor (TNF, tumor necrosis factor alpha, TNFα, cachexin, or cachectin) is a cell signaling protein (cytokine) ...
The resulting rapid change in viral genetics produces antigenic shifts, which are sudden changes from one antigen to another. ... such as interferon or tumor necrosis factor) produced from influenza-infected cells.[24][97] In contrast to the rhinovirus that ... The central core contains the viral RNA genome and other viral proteins that package and protect this RNA. RNA tends to be ... which is a slow change in the antigens on the viral surface over time.[80] The separation of the genome into eight separate ...
Usually, a target cell line expressing a certain surface-exposed antigen is incubated with antibody specific for that antigen. ... Furthermore, NK cells are involved in killing tumor cells and other cells that may lack MHC I on their surface, indicating a ... During replication of a virus some of the viral proteins are expressed on the cell surface membrane of the infected cell. ... The effects against solid tumors of trastuzumab and rituximab monoclonal antibodies have been shown in experiments with mice to ...
... viral antigen and viral RNA were found in macrophages in the synovial joint of a person experiencing a relapse of ... Viral antigen was detected in a muscle biopsy of a person suffering a recurrent episode of disease three months after initial ... Viral replication is highly cytopathic, but susceptible to type-I and -II interferon.[43] In vivo, in studies using living ... RT-PCR can also be used to quantify the viral load in the blood. Using RT-PCR, diagnostic results can be available in one to ...
Tumor markers. Tissue samples can be stained for the presence of PSA and other tumor markers in order to determine the origin ... Prostate specific membrane antigen is a transmembrane carboxypeptidase and exhibits folate hydrolase activity.[75] This protein ... Viral infection. Papilloma virus has been proposed in several studies to have a potential role in prostate cancer, but as of ... Eventually, the tumor may grow large enough to invade nearby organs such as the seminal vesicles or the rectum, or the tumor ...
Metastatic canine mammary tumors display increased levels of p21 in the primary tumors but also in their metastases, despite ... p21 interacts with proliferating cell nuclear antigen (PCNA), a DNA polymerase accessory factor, and plays a regulatory role in ... HIV infected individuals who naturally suppress viral replication have elevated levels of p21 and its associated mRNA. p21 ... and Platform-Matched Tumor and Normal DNA Copy-Number Profiles Uncovers Chromosome Arm-Wide Patterns of Tumor-Exclusive ...
The most accepted hypothesis is that dialogue between T-cell receptors and myelin antigens leads to an immune attack on the ... Proposed causes for demyelination include genetics and environmental factors such as being triggered by a viral infection or ... is a noninvasive analytical technique that has been used to study metabolic changes in brain tumors, strokes, seizure disorders ... These interactions between active T cells and myelin antigens provoke a massive destructive inflammatory response and promote ...
... tumors must be managed for the condition to be contained.[2] Opiates are sometimes used to treat severe pain, but in some cases ... The antibodies appear to interact with antigens in the brain neurons and the spinal cord synapses, causing a functional ...
... any antibody produced against this antigen (which mimics the self-antigens) can also, in theory, bind to the host antigens, and ... Presence of multiple uncleared viral infections due to lack of perforin are thought to be responsible. ... have been shown to both stimulate immune response to tumors in mice and to regulate immune function, delaying or preventing the ... Molecular Mimicry - An exogenous antigen may share structural similarities with certain host antigens; thus, ...
The viral envelope is made of modified Golgi membranes containing viral-specific polypeptides, including hemagglutinin.[42] ... which measured Variola virus-specific immunoglobulin and antigen were also developed to assist in the diagnosis of infection.[ ... The "dumbbell-shaped" structure inside the virion is the viral core, which contains the viral DNA; Mag. = ~370,000× ... Infectious skin disease: Viral cutaneous conditions, including viral exanthema (B00-B09, 050-059) ...
The antibody will be targeted at a preferentially expressed protein in the tumour cells (known as a tumor antigen) or on cells ... The susceptibility of an individual to liver damage can be altered by other factors such as the cancer itself, viral hepatitis ... Blood vessels in tumors are very different from those seen in normal tissues. As a tumor grows, tumor cells furthest away from ... Tumor lysis syndrome[edit]. In particularly large tumors and cancers with high white cell counts, such as lymphomas, teratomas ...
Old LJ (1985). "Tumor necrosis factor (TNF)". Science 230 (4726): 630-2. Bibcode:1985Sci...230..630O. PMID 2413547. doi:10.1126 ... a inflamación e inhibir a xénese de tumores e a replicación viral e responder á sepse por medio de células produtoras de IL1 e ... "Cytotoxicity mediated by soluble antigen and lymphocytes in delayed hypersensitivity. 3. Analysis of mechanism". J. Exp. Med. ... Tumor Necrosis Factor-alpha Medical Subject Headings (MeSH) na Biblioteca Nacional de Medicina dos EUA. ...
Shear MJ (1944). "Chemical treatment of tumors, IX: Reactions of mice with primary subcutaneous tumors to injection of a ... This section needs expansion with: Viral sepsis. You can help by adding to it. (March 2020) ... Upon detection of microbial antigens, the host systemic immune system is activated. Immune cells not only recognise pathogen- ... Infections leading to sepsis are usually bacterial but may be fungal or viral.[21] Gram-positive bacteria were the primary ...
Anti-tumor immune responses place cancer cells under selective pressure to lose or downregulate target antig … ... Immunotherapeutic treatments in head and neck cancer clinical trials include cancer vaccines targeting foreign viral antigens ... Anti-tumor immunity induced by ectopic expression of viral antigens is transient and limited by immune escape Oncoimmunology. ... Herein, we demonstrate the impact of immunogenic viral antigens on anti-tumor response and immune editing in MOC2-E6E7, a ...
Viral, Tumor" by people in this website by year, and whether "Antigens, Viral, Tumor" was a major or minor topic of these ... "Antigens, Viral, Tumor" is a descriptor in the National Library of Medicines controlled vocabulary thesaurus, MeSH (Medical ... Below are the most recent publications written about "Antigens, Viral, Tumor" by people in Profiles. ... Below are MeSH descriptors whose meaning is more general than "Antigens, Viral, Tumor". ...
These formulations generally comprise hybridoma of at least one antigen presenting cell ... Formulations comprising combinations of APCs and tumor cells and APCs and virally infected cells are disclosed. ... The fused cells and/or co-cultured cells are then used to provide a complete array of tumor antigens or viral antigens that can ... This is presumably because the tumor cells and viral cells are incapable of providing the antigen or antigens in the ...
MSC pulsed with peptides from viral antigens evoked … ... immunosuppressive and poorly immunogenic but may act as antigen ... In conclusion, human MSC can process and present HLA class I-restricted viral or tumor antigens to specific CTL with a limited ... MSC transfected with tumor mRNA or infected with a viral vector carrying the Hepatitis C virus NS3Ag gene induced cytokine ... of human mesenchymal stem cells in HLA-class I-restricted T-cell responses against viral or tumor-associated antigens Stem ...
Immunological detection of viral large T antigen identifies a subset of Merkel cell carcinoma tumors with higher viral ... Immunological detection of viral large T antigen identifies a subset of Merkel cell carcinoma tumors with higher viral ... 2010). Immunological detection of viral large T antigen identifies a subset of Merkel cell carcinoma tumors with higher viral ...
In this study, we measured T-cell responses against viral (n = 3) and tumor antigens (n = 47) from TILs derived from 21 MCC ... Finally, we show that MAGE-A3 antigen, frequently expressed by MCC tumors, was recognized by CD8 TILs from a virus-negative MCC ... whereas immune responses directed against shared cellular tumor-specific antigens have not been evidenced. ... and we identified two new HLA-peptide complexes derived from the LT antigen, located in a region encompassing 3 previously ...
Vaccinia virus expressing ICP47 : a novel platform for cancer vaccines highlighting tumor epitopes and hiding viral antigens ... Vaccinia virus expressing ICP47 : a novel platform for cancer vaccines highlighting tumor epitopes and hiding viral antigens. ... poxviruses or immunodominance of viral antigens which may reduce the induction of immune response against weaker tumor antigens ... Recombinant poxviruses expressing tumor associated antigens (TAAs) are evaluated since 20 years as immunogenic vaccine vector ...
Landscape of Tumor Antigens in T Cell Immunotherapy. Sadia Ilyas and James C. Yang. J Immunol 2015 195: 5117-5122 ... Vaccines against Respiratory Viral Pathogens for Use in Neonates: Opportunities and Challenges. Martha A. Alexander-Miller. J ... Unique Human Tumor Antigens: Immunobiology and Use in Clinical Trials. Giorgio Parmiani, Annamaria De Filippo, Luisa Novellino ... Tumor Stress Inside Out: Cell-Extrinsic Effects of the Unfolded Protein Response in Tumor Cells Modulate the Immunological ...
... viral antigens; antigens associated with autoimmune disease; allergens; tumor antigens; streptococcus Group B antigen; HIV I or ... viral antigens; antigens associated with autoimmune disease; allergens; tumor antigens; streptococcus Group B antigen; HIV I or ... an antigen derived from microorganisms; a hapten, a drug of abuse; a therapeutic drug; an environmental agent; and antigens ... an antigen derived from microorganisms; a hapten, a drug of abuse; a therapeutic drug; an environmental agent; antigens ...
Viral antigen recall. The IFNγ ELISPOT assay was performed on blood samples from 17 patients. Results of testing using the ... of cells along the margins of tumor nodules that extended into the tumor parenchyma and clearly involved labeling of tumor ... Viral antigen recall. The interferon gamma (IFNγ) enzyme-linked immunospot (ELISPOT) assay was performed to assess the effect ... Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc Natl ...
Fully human antibodies against a specific antigen can be prepared by administering the antigen to a transgenic animal which has ... tumor antigens; allergens; viral proteins; toxins; blood factors; enzymes; ganglioside GD3, ganglioside GM2; LMP1, LMP2; ... tumor antigens, such as her2-neu, mucin, CEA and endosialin; allergens, such as house dust mite antigen, lol p1 (grass) ... histocompatibility antigens, such as MHC class I or II, the Lewis Y antigens, Slex, Sley, Slea, and Selb; ...
Viral Recombinant Vaccines to the E6 and E7 Antigens of HPV-16 ... Curing tumor-bearing mice by shifting a Th2 to a Th1 anti-tumor ... Human papillomavirus type 16 nucleoprotein E7 is a tumor rejection antigen. L P Chen, E K Thomas, S L Hu, I Hellström, K E ... Human papillomavirus type 16 nucleoprotein E7 is a tumor rejection antigen. L P Chen, E K Thomas, S L Hu, I Hellström, K E ... Human papillomavirus type 16 nucleoprotein E7 is a tumor rejection antigen. L P Chen, E K Thomas, S L Hu, I Hellström, and K E ...
Tumor Virus Infections/immunology. Substance. *Antigens, Viral, Tumor. Grant support. *R01-CA63113/CA/NCI NIH HHS/United States ... The SV40 early region encodes three tumor antigens, large T (LT), small T (ST) and 17KT that contribute to cellular ... Large (LT), 17KT and Small (ST) of SV40 and PY as well as Middle (MT) T antigens from PY share coding regions. The N terminal ... Cellular transformation by Simian Virus 40 and Murine Polyoma Virus T antigens.. Cheng J1, DeCaprio JA, Fluck MM, Schaffhausen ...
WDFY4 is required for cross-presentation in response to viral and tumor antigens ...
Weil, R., 1978, Viral "tumor antigens"? A novel type of mammalian regulatory protein, Biochim. Biophys. Acta 516:301-308.Google ... Rifkin, D. B., Crowe, R. M. ,and Pollack, R., 1979, Tumor promoters induce changes in the chickGoogle Scholar ... Wigler, M. ,and Weinstein, I. B., 1976, Tumor promoter induces plasminogen activator, Nature (Lond.) 259:232-233.CrossRefGoogle ... 2: Mechanisms of Tumor Promotion and Cocarcinogenesis (T. J. Slaga, A. Sivak, and R. K. Boutwell, eds.), pp. 11-48, Raven Press ...
Bacterial, viral and tumour protein datasets were used to derive models for prediction of whole protein antigenicity. Every set ... The discovery of truly novel antigens will be frustrated by their lack of similarity to antigens of known provenance. To ... VaxiJen is the first server for alignment-independent prediction of protective antigens. It was developed to allow antigen ... sets for each class of antigens were used to test the stability of the discrimination between antigens and non-antigens. The ...
T Cell Responses against Viral (Tumor-Associated) Antigens in Malignant Disease. Several viruses are known to cause malignant ... cancer germ-line antigens, mutated antigens, and viral antigens (reviewed in Ref. 3 ). These TAAs have facilitated the analysis ... The most widely studied tumor antigen is the melanoma differentiation antigen melanA/MART-1, against which specific T cell ... Analysis of the T cell response to tumor and viral peptide antigens by an IFNγ-ELISPOT assay. Int. J. Cancer, 71: 932-936, 1997 ...
Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 ... Acts as a tumor suppressor in many tumor types; induces growth arrest or apoptosis depending on the physiological circumstances ... br>,/br>These range from a single component such as Viral genomes to several components as in the case of eukaryotic ... Cellular tumor antigen p53Add BLAST. 386. Amino acid modifications. Feature key. Position(s). DescriptionActions. Graphical ...
Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 ... Acts as a tumor suppressor in many tumor types; induces growth arrest or apoptosis depending on the physiological circumstances ... viral process Source: Ensembl. View the complete GO annotation on QuickGO .... ,p>UniProtKB Keywords constitute a ,a href="http ... Cellular tumor antigen p53Add BLAST. 393. Amino acid modifications. Feature key. Position(s). DescriptionActions. Graphical ...
... specific T cell responses on transplantation with hybridomas reactive to viral hemagglutinin and human tumor antigen ... specific T cell responses on transplantation with hybridomas reactive to viral hemagglutinin and human tumor antigen. In: ... peptido-mimics of antigen to T helper cells through class II MHC and de novo synthesized peptido-mimics of antigens to CTLs. ... of Rinderpest virus and human Mucin-1 have been used as surrogate B cells to study T cell responses against the antigens. The ...
0 (Antigens, Bacterial); 0 (Antigens, Neoplasm); 0 (Antigens, Viral); 0 (Biomarkers, Tumor); 0 (CTLA-4 Antigen); 0 (Epitopes, T ... Several of the identified T-cell epitopes share similarity with common bacterial and viral antigens, suggesting the involvement ... Preventive influenza vaccines must be reformulated annually because of antigen shift and drift of circulating influenza viral ... 0 (Antigens, Bacterial); 0 (Drug Carriers); 0 (Escherichia coli Proteins); 0 (K88 antigen, E coli); 0 (Plant Lectins); 0 ( ...
... numerous viral, bacterial, and parasitic infections; numerous cancers; immunity and antigen recognition and activation; ... tumor-associated, or tumor-selective antigens should reclassify the emergence of cancer as a facet of the failed immune ... Tumor-associated stromal cells as key contributors to the tumor microenvironment. Breast Cancer Res. 2016;18(1):84. View this ... Blood-based analyses of cancer: circulating tumor cells and circulating tumor DNA. Cancer Discov. 2014;4(6):650-661.. View this ...
SARS-CoV-2 viral antigens found in non-pulmonary tissues in recovering patients A team of researchers in Singapore, led by Dr. ... Molecular clock blood test could help identify actively growing tumors in metastatic breast cancer A blood test to watch ... One of the theories under investigation is that fat cells (adipocytes) act as a reservoir for SARS-CoV-2 and increase viral ... While prostate cancer originates within the prostate, metastasis, or the spread of a tumor from the site of origin to other ...
... lysing tumor cells to release a mix of tumor and viral antigens, as well as sublethally infecting antigen-presenting cells and ... Cloning of tumor antigen complementary DNA (cDNA) and production of tumor antigen-encoding RNA were performed using standard ... DCs expressing a relevant tumor antigen) but not the negative control (DCs expressing an irrelevant tumor antigen; Fig. 6B). ... Tumor antigen-specific approaches, such as dendritic cell (DC) vaccines, aim to elicit antigen-specific antitumor immunity (3 ...
Comparison of whole tumor cell and DRibbles containing viral antigens. DRibbles refer to blebs containing short-lived proteins ... DRibble vaccines prime T cells to recognize tumor antigens that otherwise may remain "hidden" biomarkers. DRibbles are ... Surveying Tumor Microenvironments. PD-L1 expression is a biomarker of response to PD-1 blockade. "But it is not a perfect ... Tumor biomarkers act as important contextual cues or signals of cancer status. "If there are T cells infiltrating your cancer, ...
The resulting TCR-engineered T cells specifically recognized tumour antigens and mounted productive anti-tumour cell responses ... 2 using recombinant viral vectors, which do not target transgenes to specific genomic sites3,4. The need for viral vectors has ... A non-viral strategy to introduce large DNA sequences into T cells enables the correction of a pathogenic mutation that causes ... Second, we replaced the endogenous T cell receptor (TCR) locus with a new TCR that redirected T cells to a cancer antigen. ...
... a nondirect antigen-driven stimulation; a direct oncogenic role of HCV; a viral immunosuppressive effect on the tumor cells; ... Antigen drive and genetic lesions. MZ B cells are continuously exposed to exogenous antigens and have a physiologically reduced ... suggesting that tumor cells have undergone antigen selection in germinal centers.42 The presence of the so-called ongoing ... Bcl10 is involved in t(1;14)(p22;q32) of MALT B cell lymphoma and mutated in multiple tumor types. Cell 1999;96(1):35-45. ...
WDFY4 is required for cross-presentation in response to viral and tumor antigens. ... Checkpoint blockade cancer immunotherapy targets tumour-specific mutant antigens.. Gubin MM, Zhang X, Schuster H, Caron E, Ward ... Pillars Article: IFNγ and Lymphocytes Prevent Primary Tumour Development and Shape Tumour Immunogenicity. Nature. 2001. 410: ... Tumor neoantigens: building a framework for personalized cancer immunotherapy.. Gubin MM, Artyomov MN, Mardis ER, Schreiber RD. ...
In this regard, we failed to ex vivo detect CD4 T cells specific for other tumor (e.g., NY-ESO-1) or viral (e.g., HA) antigens ... where immunization of tumor-bearing animals with tumor antigen recombinant vaccinia virus resulted in the expansion of tumor- ... These features suggest that tumor progression selectively drives the amplification of memory tumor antigen-specific Tregs. ... Circulating tumor antigen-specific regulatory T cells in patients with metastatic melanoma. Proc Natl Acad Sci U S A 2007; 104 ...
  • Immunotherapeutic treatments in head and neck cancer clinical trials include cancer vaccines targeting foreign viral antigens or mutational neoantigens derived from cancer-expressed proteins. (
  • SV40 LT mediated transformation requires binding to the tumor suppressor proteins Rb and p53 in the nucleus and ST binding to the protein phosphatase PP2A in the cytoplasm. (
  • SV40 LT also binds to several additional cellular proteins including p300, CBP, Cul7, IRS1, Bub1, Nbs1 and Fbxw7 that contribute to viral transformation. (
  • Responsiveness of specific CD8+ and CD4+ T cells to viral proteins and to recombinant epitopes was monitored by MHC-multimer staining and cytokines (IFNγ & IL-2) expression analysis. (
  • Antigenic peptides derived from the encoded proteins are therefore presented on the surface of tumor cells and not on normal cells. (
  • It was developed to allow antigen classification solely based on the physicochemical properties of proteins without recourse to sequence alignment. (
  • The STag protein is expressed from a gene that overlaps the large tumor antigen (LTag) such that the two proteins share an N-terminal DnaJ-like domain but have distinct C-terminal regions. (
  • The "late region" contains genes encoding the viral capsid proteins. (
  • Viral proteins therefore promote dysregulation of the cell cycle and entry into S phase. (
  • tumour cell lines and proteins obtained. (
  • In this study, we show that the Egr2-driven cell surface proteins LAG-3 and 4-1BB can identify dysfunctional tumor antigen-specific CD8 + TIL. (
  • Finally, most tumor-associated antigens (TAAs) are derived from non-mutated self proteins, resulting in deletion of CTL with high avidity for TAAs. (
  • Using a biodegradable nanoparticle as a means of delivering tumor cell debris and proteins to the immune system, investigators at Yale University have developed a promising new method for creating therapeutic anticancer vaccines. (
  • The early region codes for proteins involved in the regulation of viral transcription (E2), viral DNA replication (E1 and E2), cell proliferation (E5, E6 and E7) and, possibly, some late steps in the viral life cycle (E4). (
  • Deficiencies or abnormalities in these proteins may lead to unregulated cell growth and tumor development. (
  • One approach to cancer vaccination is to separate proteins from cancer cells and immunize patients against those proteins as antigens, in the hope of stimulating the immune system to kill the cancer cells. (
  • Cancer vaccines seek to target a tumor-specific antigen and distinct from self-proteins. (
  • In NPC, EBV infection has type II latency mechanism [ 6 ], which is featured by several noncoding RNAs, latent membrane proteins (LMP1, LMP2A, and LMP2B), and Epstein-Barr nuclear antigen 1 (EBNA1) [ 7 ]. (
  • But in Wallace, most of the T-cells were intent on destroying abnormal proteins that were unique to her tumor. (
  • When they gve CAR-Ts that lack all three Nr4a proteins to mice, their tumors began to shrink and they lived longer. (
  • The Rao lab also found that another family of proteins called NFAT turned on Nr4a in T cells that entered tumors, suggesting that both proteins were somehow involved in wearing out cancer-fighting T cells. (
  • Indeed, the processing of proteins from internalized microorganisms to derive antigens for presentation at the cell surface on major histocompatibility complex (MHC) 1 class I and class II molecules is a key mechanism of adaptive immunity ( 3 ). (
  • The DNA tumor virus simian virus 40 produces the Large T antigen which inactivates two of the cell's most important cancer-preventing proteins, p53 and pRb. (
  • T antigen also inactivates some of the most important proteins that protect cells against malignant transformation, including tumor suppressor proteins p53 and pRb. (
  • SV40 T antigen contains a motif that mimics the destruction signal found in these proteins. (
  • The large T antigen encoded by SV40 or polyoma viruses inactivates several key proteins involved in cell cycle regulation ( DeCaprio, 1999 ). (
  • latent membrane proteins (LMP's) and EBV nuclear antigen (EBNA's). (
  • They spot their target by identifying small pieces of proteins - or antigens - at the surface of diseased cells. (
  • While the high polymorphism of these proteins ensures immune recognition of a variety of self-antigens and viral peptides, it also represents a major barrier to allo-transplantation. (
  • The purpose of T cell-mediated cancer immunotherapy is to reactivate these responses to a degree that results in tumor destruction without causing harmful effects on normal cells. (
  • Specific immunotherapy is a promising approach ( 1 - 3 ) to the treatment of a wide range of medical conditions including chronic viral diseases, autoimmune inflammatory disorders, and various types of cancer. (
  • This pronounced bias in processing and presentation of the Melan-A antigens is reminiscent of immunodominant protein regions and lends itself to detailed analysis of melanoma-specific CD8 and CD4 T-cell responses in defined clinical situations such as tumor progression, tumor cell death provoked by chemotherapy or radiotherapy, and in the course of immunotherapy. (
  • Cancer immunotherapy has focused on the identification of tumor-associated antigens that are expressed exclusively by cancer cells. (
  • Cancer immunotherapy, using a classic vaccine approach, is dependent on the induction of an immune response which is capable of killing tumor cells but inducing no, or limited, deleterious autoimmune reactions. (
  • The identification of a tumor-associated antigen which is expressed on the tumor target (both primary and metastases) but which is absent on all (or at least most) normal tissues is important for safe and targeted immunotherapy. (
  • Antigen-specific immunotherapy, combining viral tumor antigen or personalized neoepitopes with immune targeting, offers a solution. (
  • In this study, we show how highly reactive antigen (Ag)-specific CTLs can be generated from induced pluripotent stem (iPS) cells to provide an unlimited source of functional CTLs for adoptive immunotherapy. (
  • In vitro immunization and expansion of antigen-specific cytotoxic T lymphocytes for adoptive immunotherapy using peptide-pulsed dendritic cells. (
  • The design of an effective procedure to sensitize and expand antigen-specific cytotoxic T lymphocytes (CTL) in vitro is essential for the development of effective adoptive cellular immunotherapy protocols for cancer. (
  • The results and procedures described herein may facilitate the development of effective CTL-based adoptive immunotherapy for chronic viral diseases and cancer. (
  • Passive immunotherapy with monoclonal antibodies using this antigen has shown promising results. (
  • Natural killer (NK) cells have the capacity to target tumors and are ideal candidates for immunotherapy. (
  • In this study, we used trogocytosis as a non-viral method to modify NK cells for immunotherapy. (
  • Natural killer (NK) cells have the ability to recognize and eliminate tumor cells, making them ideal candidates for tumor immunotherapy [1] , [2] . (
  • CD19 is an ideal target antigen for immunotherapy because it is expressed on nearly all leukemia cells in most patients with B-cell acute lymphoblastic leukemia (ALL) and chronic lymphoblastic leukemia (CLL) [13] , [14] . (
  • With focal points of the conference including autologous tumour cell immunotherapy, combinatorial approaches (including immune checkpoint inhibitors and IDO inhibitors) and case studies of current clinical trials, this conference will provide the perfect platform to highlight emerging strategies in cancer vaccines. (
  • Therapeutic vaccination with dendritic cells (DCs) loaded with tumor antigens is an active form of immunotherapy, which intends to direct the immune system towards tumors which express the respective vaccination antigens. (
  • MOC2-E6E7 tumors demonstrated an "inflamed" or immune-activated tumor microenvironment and greater infiltration of CD8 + T cells compared to MOC2. (
  • Vaccination induced robust infiltration of antigen-specific CD8 + T cells, which led to tumor growth delay and modestly prolonged survival in MOC2-E6E7 tumors. (
  • Role of the amino-terminal domain of simian virus 40 early region in inducing tumors in secretin-expressing cells in transgenic mice. (
  • Formulations comprising combinations of APCs and tumor cells and APCs and virally infected cells are disclosed. (
  • These formulations generally comprise hybridoma of at least one antigen presenting cell fused to either at least one tumor cell or at least one virally infected cell, or the products of co-cultures of antigen presenting cells and either tumor cells or virally infected cells. (
  • wherein said first cells are antigen presenting cells selected from the group consisting of macrophages, B-cells and dendritic cells, and said second cells are selected from the group consisting of tumor cells and virally infected cells. (
  • 15. The formulation of claim 13, wherein said tumor cells are selected from the group consisting of melanoma cells, lung carcinoma cells, sarcomas, prostate carcinoma cells, breast carcinoma cells, colon carcinoma cells and cervical carcinoma cells. (
  • In order to highlight in vitro the immunogenic advantage provided by ICP47 blockade of viral epitopes, T cells were pre-sensitized with WT-VV infected APC and then used as responders to r.VV-Mart-US12 or r.VV-Mart infected APC. (
  • Cells infected with HSV-US12-r.VV, demonstrated a decreased ability of presenting MHC class-I antigens to CD8+ T cells whereas MHC-class-II restricted presentation to CD4+ T cells remained unaffected. (
  • T lymphocytes are cells of the immune system that attack and destroy virus-infected cells, tumor cells and cells from transplanted organs. (
  • Whereas each T cell recognizes a single antigen, collectively the T cells are endowed with a large diversity of receptors targeted at a wide variety of antigens. (
  • There a process named central tolerance eliminates the T cells that have a receptor recognizing an antigen present on normal cells of the organism. (
  • This enables the T cells to eliminate cells with "foreign" or "abnormal" antigens without harming the normal cells. (
  • It has long been debated whether cancer cells were bearing "tumor-specific" antigens, absent from normal cells, which could in principle cause the elimination of the tumor by the immune system. (
  • Hence, a new antigen is present only on the tumor cells. (
  • The recognition of mutation-induced antigens on tumors by T cells is only one aspect of a more general phenomenon which can rightly be named: T cell immunosurveillance of the integrity of the genome. (
  • Any somatic mutation has a probability of producing a new antigen that can be recognized by T cells. (
  • Some genes are expressed by tumor cells and not by normal cells. (
  • A class of genes, named cancer-germline genes, is expressed in a large variety of cancer cells but not in normal cells, with the exception of germline cells, which do not carry MHC molecules on their surface and therefore do not present the antigens. (
  • The transformed cells often express permanently some viral genes. (
  • This leads to the presentation of viral antigenic peptides absent from normal cells. (
  • In some patients, the majority of the tumor-specific T cells recognize mutated antigens. (
  • determined that PVSRIPO stimulates anticancer immunity by two mechanisms: lysing tumor cells to release a mix of tumor and viral antigens, as well as sublethally infecting antigen-presenting cells and thereby stimulating an interferon-driven immune response in the tumor microenvironment. (
  • At the same time, sublethal infection of antigen-presenting cells, such as dendritic cells and macrophages, yields potent, sustained type I interferon-dominant activation in an immunosuppressed microenvironment and promotes the development of tumor antigen-specific T cell responses in vitro and antitumor immunity in vivo. (
  • The tumor microenvironment favors tumor immune escape by suppressing production, activation, and/or function of antitumor T cells. (
  • This is the first report on direct ex vivo identification of antigen-specific FOXP3+ T cells by multimer labeling in cancer patients and on the direct assessment of the impact of peptide vaccination on immunoregulatory T cells. (
  • The discovery of tumor-associated antigens recognized by conventional αβ T cells provided the foundation for the design of defined antigen-based cancer vaccines ( 4 ). (
  • Phosphoantigen surveillance by T cells has been observed in major histocompatibility complex (MHC) class I- and class II-restricted antigen presentation ( , 8 - , 10 ). (
  • Many of these antigens are not expressed on the surface of tumor cells, and therefore are not directly accessible to antibodies. (
  • Additionally, when tumor cells are transfected with 5T4 cDNA, they display increased motility, suggesting that expression of this molecule may induce metastatic properties in a tumor ( 6 , 7 ). (
  • One possible way to induce a potent and targeted antitumor response is to use viruses to deliver the tumor-associated antigen to cells of the immune system. (
  • Transfection of tumor cells with 5T4 cDNA results in increased cell motility, suggesting that expression of this molecule may induce metastatic properties ( 7 , 8 ). (
  • Here we present a nanoparticle delivery system that facilitates presentation of an immunogenic measles antigen specifically in cancer cells. (
  • Treatment with this system facilitates activation of a secondary immune response against cancer cells, bypassing the need to identify tumor-associated antigens or educate the immune system through a primary immune response. (
  • Specifically expressed sugar chains on adult T-cell leukemia(ATL) cells should be tumor markers,which can be appropriate antigen molecules in the targeted therapy using ant ibodies.Trace amount of sugar chains extracted and fractionated from tumor ATL cells were immobilized on the top of the optical fiber(50) chemically modified with gold nanoparticles to prepare fiber-type sugar chip. (
  • However, the lack of flexible systems targeting tumor antigens to cross-presenting dendritic cells (DCs) limits clinical development. (
  • In patients with advanced melanoma, we have previously shown that the cancer-germline antigen NY-ESO-1 stimulates spontaneous NY-ESO-1-specific CD8 + T cells that up-regulate PD-1 expression. (
  • In addition, Tim-3-Tim-3L blockade enhanced cytokine production and proliferation of NY-ESO-1-specific CD8 + T cells upon prolonged antigen stimulation and acted in synergy with PD-1-PD-L1 blockade. (
  • We observed that PD-1 up-regulation on spontaneous NY-ESO-1-specific CD8 + T cells occurs along with T cell activation and is not directly associated with an inability to produce cytokines ex vivo upon stimulation with cognate antigen. (
  • Blockade of the PD-1-programmed death ligand 1 (PD-L1) pathway in combination with prolonged antigen stimulation with PD-L1 + APCs or melanoma cells augmented the frequencies of cytokine-producing, proliferating, and total NY-ESO-1-specific CD8 + T cells. (
  • To further determine whether other molecular pathways are involved in tumor antigen-specific T cell dysfunction, we studied T cell immunoglobulin and mucin-domain-containing molecule 3 (Tim-3) expression on spontaneous NY-ESO-1-specific CD8 + T cells from patients with advanced melanoma and investigated whether Tim-3 up-regulation defines a subgroup of dysfunctional tumor antigen-specific CD8 + T cells. (
  • Our results indicate that coexpression of LAG-3 and 4-1BB characterize dysfunctional T cells within tumors, and that targeting these receptors has therapeutic utility. (
  • A deeper understanding of this putative T cell-intrinsic defect should lead to further improvements of immunotherapies aimed at restoring the function of those T cells to ultimately support tumor rejection ( Gajewski, 2007b ). (
  • B cell hybridomas expressing class I and II MHC molecules and producing antibodies directed against hemagglutinin protein of Rinderpest virus and human Mucin-1 have been used as surrogate B cells to study T cell responses against the antigens. (
  • The observed CTL and lymphoproliferative response indicates that anti-idiotypic B cells termed Jerne cells stimulate both T helper and T cytotoxic cells by virtue of their ability to present recycled or regurgitated peptido-mimics of antigen to T helper cells through class II MHC and de novo synthesized peptido-mimics of antigens to CTLs. (
  • Furthermore, differences in the repertoire of subdominant antigen-specific T-cells were also detected, suggesting that antigen-encounter in vivo can shape the immune response. (
  • Several of the identified T-cell epitopes share similarity with common bacterial and viral antigens, suggesting the involvement of pre-existing microbial cross-reactive T cells in rapid and durable tumour regression seen in some patients. (
  • Most importantly, adoptive transfer of TCR-transduced iPS cells triggered infiltration of OVA-reactive CTLs into tumor tissues and protected animals from tumor challenge. (
  • CTLs can target malignant tumors by T-cell receptor (TCR) and release cytotoxins as well as cytokines to kill tumor cells. (
  • We found that these iPS cells differentiated into functional Ag-specific CTLs in vivo and significantly protected the hosts from a tumor challenge. (
  • Expression and disposition of the murine mammary tumor virus (MuMTV) envelope gene products by murine mammary tumor cells. (
  • The purpose of this study is to characterize the molecular and cell biology of the tumor cells in lymphoma. (
  • One of the theories under investigation is that fat cells (adipocytes) act as a reservoir for SARS-CoV-2 and increase viral load in obese or overweight individuals. (
  • Chemotherapy kills rapidly dividing cancer cells, but it also damages healthy cells in the body and often does not effectively prevent tumor metastasis or disease recurrence. (
  • Focal staining showed this antigen to be present in epidermal cells in 12 of 16 skin biopsy specimens. (
  • Knowing if therapeutic strategies have worked will likely require measurement of immune-response molecules, rather than genetic analysis of tumor cells. (
  • Protection in gp70-deficient mice correlated with more robust gp70-specific CTL responses, and increased numbers and avidity of responding antigen-specific T cells after vaccination. (
  • Tumor-associated macrophages, myeloid-derived suppressor cells, and regulatory T cells reduce effector functions of tumor-specific CTL. (
  • In addition, tumor cells secrete inhibitory cytokines and produce other factors associated with chronic inflammation that reduce antitumor responses. (
  • Thus, the T cells that may be most effective against tumors are deleted during negative selection in the thymus [ 5 - 7 ]. (
  • Experiments using transgenic mice expressing T cell receptor (TCR) genes and transfected TAAs have elucidated many of the obstacles that prevent the development and function of tumor-reactive T cells. (
  • The influence of antigen-specific tolerance varies depending on the number and source of T cells [ 8 , 9 ]. (
  • In polyclonal systems, T cell function varies with the diversity of the repertoire, the avidity for antigen-presenting cells, and the precursor population size [ 12 - 14 ]. (
  • Many studies use transplantable tumors transfected with model antigens so that either transferred T cells or endogenous responses can be monitored [ 15 , 16 ]. (
  • The B cells resident in the MZ function as innate-like lymphocytes that mount rapid antibody responses to both T-cell-dependent and -independent antigens. (
  • Post-germinal center memory B cells, needed for the T-cell-dependent immune response, are also localized in the MZ, as well as a variety of other immune system cells (plasma cells, dendritic cells, macrophages, T cells, and granulocytes) that interact with circulating antigens. (
  • T cells engineered to express chimeric antigen receptors (CARs) have established efficacy in the treatment of B-cell malignancies, but their relevance in solid tumors remains undefined. (
  • Here we report results of the first human trials of CAR-T cells in the treatment of solid tumors performed in the 1990s. (
  • Patients with metastatic colorectal cancer (CRC) were treated in two phase 1 trials with first-generation retroviral transduced CAR-T cells targeting tumor-associated glycoprotein (TAG)-72 and including a CD3-zeta intracellular signaling domain (CART72 cells). (
  • The authors describe the first human application of autologous chimeric antigen receptor gene-modified T cells targeting TAG-72 in the treatment of metastatic colorectal cancer in two clinical trials. (
  • The absence of detectable viral antigen-positive cells in previous reports may relate to the fact that the patients died during the late phase of the disease after intensive treatment with antiviral drugs. (
  • Different assays are now available that can detect small amounts of HPV DNA, quantify the amount of viral DNA in clinical specimens, identify a broad spectrum of genital and cutaneous HPV types, test for selected HPV types and localize the viral genome and viral transcripts to individual cells. (
  • PURPOSE: Colorectal carcinoma cells express the tumor-associated antigen epithelial cellular adhesion molecule (Ep-CAM)/KSA. (
  • Viral vectors have been used to genetically modify in vitro expanded NK cells to express chimeric antigen receptors (CARs), which confer cytotoxicity against tumors. (
  • We have previously genetically modified in vitro expanded NK cells to express DAP10 and the chimeric NKG2D receptor containing the CD3ζ signal domain, which altered the balance between the activating and inhibitory signals of NK cells and enhanced the cytotoxicity against NKG2D ligand-bearing tumors [3] . (
  • Further, expression of anti-CD19 chimeric antigen receptors (CARs) containing 41BB and CD3ζ signal domains on NK cells enhanced the activating signals originating from CD19 antigen engagement, leading to cytotoxicity specifically against B-cell leukemia [4] . (
  • Similarly, T cells captured NKG2D and NKp46 ligands on tumor cells through trogocytosis and promoted NK cell activity [12] . (
  • The large tumor antigen (LTag) of simian virus 40, an AAA(+) protein, is a hexameric helicase essential for viral DNA replication in eukaryotic cells. (
  • Here we show that HAdV-2 gene expression and progeny formation in NMuMG cells transformed with the SV40 T antigen (NMuMG-T cells) were as efficient as in the parental NMuMG cells. (
  • We are developing a novel strategy for targeting B cell lymphoma tumor cells by activating Epstein Barr virus (EBV)-specific T cells (Yu, Ilecka et al. (
  • Here the tumor cells are used as antigen-presenting cells that present EBV antigens and are recognized by EBV-specific T cells (Figure 1). (
  • This is followed by uptake of the AgAbs by the tumor cells wherein they are processed into smaller peptides, which are then presented on the surface of the B cells to T cells in the context of MHC molecules. (
  • EBV-specific T cells from these patients are expanded and their ability to mount an immune response against CLL cells exposed to antibodies loaded with EBV antigens is tested in cytokine release assays and killing assays. (
  • Figure 1: Principle of AgAb-mediated tumor killing The rationale behind this strategy is to force tumor cells to act as an antigen-presenting cell. (
  • The antibodies bind to B cell lymphomas, are internalized, processed and the viral antigens are presented at the surface of the tumor cells. (
  • An antibody is a protein (immunoglobulin) produced by B-lymphocytes (immune cells) in response to stimulation by an antigen. (
  • Selection of the appropriate adjuvant to activate antigen-presenting cells to stimulate immune responses, is required. (
  • NK cells provide rapid responses to virus-infected cells, acting at around 3 days after infection , and respond to tumor formation. (
  • In contrast to NKT cells, NK cells do not express T-cell antigen receptors (TCR) or pan T marker CD3 or surface immunoglobulins (Ig) B cell receptors , but they usually express the surface markers CD16 (FcγRIII) and CD56 in humans, NK1.1 or NK1.2 in C57BL/6 mice . (
  • Efficient vaccination against infectious agents and tumors depends on specific antigen targeting to dendritic cells (DCs). (
  • We report here that biosafe coronavirus-based vaccine vectors facilitate delivery of multiple antigens and immunostimulatory cytokines to professional antigen-presenting cells in vitro and in vivo . (
  • Furthermore, human DCs transduced with Melan-A-recombinant human coronavirus 229E efficiently activated tumor-specific CD8 + T cells. (
  • This study describes a novel vaccine approach that facilitates delivery of viral or tumor antigens to dendritic cells in vivo . (
  • Single immunization with only low doses of coronavirus-based vaccine vectors was sufficient to elicit (i) vigorous expansion and optimal differentiation of CD8 + T cells, (ii) protective and long-lasting antiviral immunity, and (iii) prophylactic and therapeutic tumor immunity. (
  • Moreover, highly efficient antigen delivery to human DCs with recombinant human coronavirus 229E and specific stimulation of human CD8 + T cells revealed that this approach is exceptionally well suited for translation into human vaccine studies. (
  • There is compelling evidence that CD8 + cytotoxic T cells are crucial players in the protective immune response against viral infections and tumors ( 4 ). (
  • The human immunodeficiency virus binds to this antigen and infects and kills T cells bearing this antigen, thus gradually destroying the body's ability to resist infection. (
  • class II a's major histocompatibility antigens found only on immunocompetent cells, primarily B lymphocytes and macrophages. (
  • 4. Role of plasmacytoid dendritic cells in the induction and regulation of anti-tumor responses. (
  • 8. Presentation of bacterial and viral antigens by antigen-presenting T cells. (
  • and the cytotoxicity and receptor binding activities of the TNF are unaffected or enhanced on tumor cells. (
  • In both mouse experiments and human clinical trials, the vaccines created abundant T cells specialized to find the antigen and destroy cells that have it. (
  • These T cells were easily observed in the bloodstream, yet there was little or no effect on tumors in the vast majority of cases. (
  • We discovered that only a few T cells actually get to the tumor, while many more are stuck or double back to the vaccination site," Overwijk says. (
  • Saline-based vaccine puts 30 times more T cells on tumor Cell fluorescence analysis of melanoma tumors in mice showed a 30-fold increase in T cells at the tumor site for those receiving saline-based vaccine compared with those who got an IFA-based vaccine. (
  • A separate experiment using flow cytometry confirmed the accumulation of T cells in the tumor and minimal presence at the injection site in those injected with saline-based vaccine. (
  • A closer examination of why Scott's cells worked so well has also led to a new discovery that may be helpful in killing other kinds of solid tumors. (
  • A person's immune system will naturally try to kill off any invader, including cancer, but usually falls short because tumors can mutate, hide, or simply overpower the white blood cells that lead the attack, known as T-cells. (
  • Immunotherapies that have seen widespread success, such as chimeric antigen receptor (CAR-T) cell therapies, mainly target blood cancers like lymphoma, myeloma and leukemia, which have a tumor antigen - like a flag or a signal - on the surface of the cells so it is easy for immune cells to find and target the harmful cells. (
  • In Scott's trial, the strategy was to surgically remove one of her tumors, and isolate the T-cells that were already trying to attack it. (
  • And in Scott, about two-thirds of the cells that cleared away her cancer were all targeting another tumor signal, a protein called KK-LC-1. (
  • As you contract a viral illness, the pathogen infects your cells. (
  • The white blood cells attack the viral cells and destroy them, thus clearing the virus from your body. (
  • Before moving further into a discussion of the benefits of colostrum, it's important to identify the function of NK cells in the immune system and in the prevention of viral diseases and tumors, as this is the foundation of many of the benefits of colostrum. (
  • Natural killer (NK) cells are effector lymphocytes of the innate immune system that control several types of tumors and microbial infections by limiting their spread and subsequent tissue damage … NK cells can thus limit or exacerbate immune responses. (
  • The process of targeting and killing aberrant viral and tumor cells is mediated by molecules stored in a secretory lysosome, or specialized organelle, found in the NK cells. (
  • However, NK cells are not antigen-specific, a process used by your humoral immune response. (
  • Instead the NK cells help reduce viral replication as the adaptive arm of your immune system creates antibodies. (
  • A deficiency in NK cells may leave you susceptible to viral infections and, potentially, tumor formation. (
  • 7 , 8 Although not antigen-specific, NK cells differentiate between normal healthy cells and aberrant cells, leading scientists to seek ways to enhance NK cell function as a way of improving the effectiveness of cancer treatments. (
  • Scientists at La Jolla Institute found that blocking Nr4a transcription factors could improve CAR-T cells' efficacy in solid tumors. (
  • The immune system maintains a balance between immune response and immune tolerance, but that balance can tip toward the latter when T cells are exposed to chronic infection or the tumor microenvironment-a phenomenon known as "T cell exhaustion. (
  • The team, led by LJI researcher Anjana Rao, Ph.D., previously observed increased levels of Nr4a in T cells that fight chronic viral infections. (
  • Over time, those T cells seemed to grow tolerant to the viral antigens and stopped working. (
  • In tumor-bearing mouse models, the experimental CAR-T cells promoted tumor regression and kept most of the mice alive over the 90-day study period, while the rodents that got normal CAR-Ts died of cancer by day 35, according to the team. (
  • Moreover, the modified CAR-Ts showed greater anti-tumor activity than did similar cells that were only lacking one Nr4a protein. (
  • Tumor necrosis factor (TNF) receptor 6/decoy receptor 3 (TR6/DcR3) is an antiapoptosis soluble receptor of the TNF family produced by tumor cells. (
  • TR6 mRNA and protein were detectable in selected antigen-presenting cells. (
  • Monocytes and myeloid-derived dendritic cells (MDC) released the protein exclusively following stimulation of Toll-like receptor 2 (TLR2) and TLR4 by gram-positive and gram-negative bacterial antigens. (
  • Plasmacytoid dendritic cells, activated by bacterial antigens via TLR9 or by viral infection, did not produce the protein. (
  • Because of TR6 overexpression in a substantial number of tumors ( 23 , 28 ), it has been postulated that the decoy receptor promotes the survival of tumor cells by helping them to escape FasL-dependent cell death ( 3 , 25 ). (
  • Macrophages play an important role in innate and adaptive immunity as professional phagocytes capable of internalizing and degrading pathogens to derive antigens for presentation to T cells. (
  • Here, we designed recombinant measles vaccine vectors for priming and activation of antigen-specific CD8+ T cells. (
  • We previously demonstrated that tumor irradiation potentiates cancer vaccines using genetic modification of tumor cells in murine tumor models. (
  • To investigate whether tumor irradiation augments the immune response to MUC1 tumor antigen, we have tested the efficacy of tumor irradiation combined with an MVA-MUC1-IL2 cancer vaccine (Transgene TG4010) for murine renal adenocarcinoma (Renca) cells transfected with MUC1. (
  • Generation of tumor-specific T cells was detected by IFN-γ production from splenocytes stimulated in vitro with tumor lysates using ELISPOT assays. (
  • Responding mice were immune to challenge with Renca-MUC1 cells, indicating the induction of specific tumor immunity. (
  • Histology studies of regressing tumors at 1 week after therapy, revealed extensive tumor destruction and a heavy infiltration of CD45 + leukocytes including F4/80 + macrophages, CD8 + cytotoxic T cells and CD4 + helper T cells. (
  • The generation of tumor-specific T cells by combined therapy was confirmed by IFN-γ secretion in tumor-stimulated splenocytes. (
  • Cancer vaccines are designed to promote tumor specific immune responses, particularly cytotoxic CD8 positive T cells that are specific to tumor antigens. (
  • After 2-3 rounds of stimulation, the T-cells from 11 out of 13 healthy donors recognized the antigen. (
  • 2015. Development of an Ad5 vector pseudotyped with Ad48 knob protein and targeted to αvβ6 integrin efficiently targets tumour cells and evades pre-existing immunity in clinical ascites . (
  • If the binding surfaces are complementary, and the T cells can effectively bind to the antigen, then it can set into motion the immunological cascade which eventually results in the destruction of the pathogen. (
  • It results in the production of thousands of identical cells, all of which are specific for the original antigen. (
  • The large clone of identical lymphocytes then differentiates into different cells that can destroy the original antigen. (
  • The T-8 lymphocytes differentiate into cytotoxic T-lymphocytes (CTLs) that can destroy the body cells that have the original antigenic epitope on its surface, e.g., bacterial infected cells, viral infected cells, and tumor cells. (
  • These cells are capable of remembering the original antigen. (
  • Certain other cells known as the T-8 suppressor cells play a role in turning off the immune response once the antigen has been removed. (
  • Using TCR transgenic cells specific for the malaria circumsporozoite protein, a leading vaccine candidate, we found that sporozoite antigen persists for over 8 weeks after immunization-a remarkable finding since irradiated sporozoites are incapable of replication and do not differentiate beyond early liver stages. (
  • Persisting antigen was detected in lymphoid organs and depends on the presence of CD11c+ cells. (
  • Firstly, reducing the time primed CD8+ T cells were exposed to antigen in vivo severely reduced the final size of the developing memory population. (
  • Finally, persisting antigen was able to prime naïve cells, including recent thymic emigrants, to become functional effector cells capable of eliminating parasites in the liver. (
  • Following initial antigen exposure CD8+ T cells expand into effector cells before forming a numerically stable memory population, a process that has been characterized as T cells on "autopilot" [9] . (
  • In the longer term, persisting antigen during chronic viral infection is often considered detrimental to T cell immunity as over-stimulated T cells may become exhausted and lose effector function [10] , [11] . (
  • Tumors often co-exist with T cells that recognize somatically mutated peptides presented by cancer cells on major histocompatibility complex I (MHC-I). However, it is unknown why the immune system fails to eliminate immune-recognizable neoplasms before they manifest as frank disease. (
  • Surprisingly, we show that immunogenic tumor antigens do not lead to immune-mediated cell rejection when the fraction of cells bearing each antigen ('clonal fraction') is low. (
  • These data indicate that tumor neoantigen heterogeneity has an underappreciated impact on immune elimination of cancer cells and has implications for the design of immunotherapeutics such as cancer vaccines. (
  • T cells are specialized agents of the immune system that can detect and attack tumors. (
  • Yet, cells that become cancerous and start displaying suspicious antigens can manage to escape T cells and grow into full tumors. (
  • One possibility is that T cells do not identify certain antigens carried by cancer cells. (
  • To test this, researchers have conducted experiments where they inject a mouse with cancer cells that display a single new antigen. (
  • developed a new technique, PresentER, where a rodent gets injected with a mix of millions cancer cells that each displays a different antigen. (
  • The tumors are left to grow for several weeks before they are removed and analyzed to see which cells survived and which have been killed by the immune system. (
  • Instead, cancer cells with new antigens could go undetected if they were rare and made up only a small proportion of all the different cancer cells in a tumor. (
  • Yet, the existence of T cells that recognize neoantigens is often not sufficient to eliminate tumors. (
  • Thus, tumor-specific T cells can lead to tumor rejection in a new host or when used as a cancer therapy, but somehow immune surveillance is evaded during early tumorigenesis in the host that originally developed an immunogenic tumor. (
  • This is based on the presence of high numbers of tumour infiltrating T cells in tumour tissue, the correlation between the density of lymphatic infiltrates in tumour lesions and prognosis and, probably most importantly, the finding that adoptive immune therapy may lower post-surgical recurrence rates in humans. (
  • Their ubiquitous expression regulates many cellular immune responses, from thymic selection to presentation of endogenous peptides, for efficient eradication of virus-infected or tumor cells ( 1 ). (
  • In support of this hypothesis, it was demonstrated that presentation of HLA-G on target cells downregulates effector functions in NK cells, antigen-specific CD8 + T cells, and monocytes through engagement of inhibitory receptors expressed on effector cells ( 5 - 9 ). (
  • Thus, unlike polymorphic class Ia HLA molecules, which have evolved as efficient activators of immune responses, presentation of HLA-G may have specialized to increase the activation/effector thresholds of T-, NK, and antigen-presenting cells for the immune protection of the semiallogeneic fetus and certain autologous tissues. (
  • Hence, it was shown that transgenic expression of viral antigens within pancreatic islets does not elicit an immune response even in the face of circulating autoreactive T-cells ( 10 ). (
  • We now appreciate that the immune system plays a dual role in cancer: It can not only suppress tumor growth by destroying cancer cells or inhibiting their outgrowth but also promote tumor progression either by selecting for tumor cells that are more fit to survive in an immunocompetent host or by establishing conditions within the tumor microenvironment that facilitate tumor outgrowth. (
  • Some investigators argued that tumor cells did not possess the appropriate "danger signals" needed to alert the immune system to the presence of a foreign cell ( 7 ), whereas others suggested that the immune system would ignore or be tolerant to a developing tumor because tumor cells were too similar to the normal cells from which they were derived ( 8 ). (
  • In contrast, tumor growth remained similar in Rag1 -/- mice lacking adaptive immunity. (
  • Some caveats for using recombinant viral vector are due to either prior systemic immunity to poxviruses or immunodominance of viral antigens which may reduce the induction of immune response against weaker tumor antigens. (
  • Phosphorylation plays a critical cellular role, and deregulation in phosphate metabolism is associated with disease, including autoimmunity and tumor immunity. (
  • We have solved the high-resolution structures of 3 HLA A2-restricted phosphopeptides associated with tumor immunity and compared them with the structures of their nonphosphorylated counterparts. (
  • Thus, cross-presenting DCs targeted with antigen-Clec9A-TNE stimulate therapeutically effective tumor-specific immunity, dependent on T cell help. (
  • However, TCD substantially impairs post-transplant anti-viral and anti-tumor immunity ( 4 - 6 ). (
  • In vitro demonstration of humoral and cell-bound immunity against common specific transplantation atigen(s) of adenovirus 12-induced mouse and hamster tumors. (
  • Taken together, this novel vaccine platform is well suited to deliver antigens and immunostimulatory cytokines to DCs and to initiate and maintain protective immunity. (
  • IFA sticks around the vaccination site for up to three months, along with the antigen designed to trigger immunity against the tumor," Overwijk says. (
  • They also produce pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-α) that mediate local and systemic responses and direct the development of adaptive immunity. (
  • Jäger Ungerechts Engeland Priming and activation of CD8+ T cell responses is crucial to achieve anti-viral and anti-tumor immunity. (
  • These findings suggest that cancer vaccine given prior to local tumor irradiation augments an immune response targeted at tumor antigens that results in specific anti-tumor immunity. (
  • Together these data show that the optimal development of protective CD8+ T cell immunity against malaria liver stages is dependent upon the prolonged presentation of sporozoite-derived antigen. (
  • This protein down-regulates MHC class-I antigen presentation by blocking the transporter associated with antigen processing (TAP), which translocates peptides, generated by proteasomal protein degradation, into the endoplasmic reticulum for loading onto MHC class I molecule. (
  • To overcome the limitations of alignment-dependent methods, we propose a new alignment-free approach for antigen prediction, which is based on auto cross covariance (ACC) transformation of protein sequences into uniform vectors of principal amino acid properties. (
  • Bacterial, viral and tumour protein datasets were used to derive models for prediction of whole protein antigenicity. (
  • The small tumor antigen (also called the small T-antigen and abbreviated STag or ST) is a protein encoded in the genomes of polyomaviruses, which are small double-stranded DNA viruses. (
  • The C-terminal portion of the STag protein is distinct from LTag but shares an additional ~100 residues with middle tumor antigen in those viruses that express it, such as murine polyomavirus. (
  • The first vaccination strategy involved immunization with the recombinant tumor-associated protein, carcinoembryonic antigen (CEA). (
  • The large tumor antigen: a 'Swiss Army knife' protein possessing the functions required for the polyomavirus life cycle. (
  • This approach was used in the drug talimogene laherparepvec , a version of herpes simplex virus engineered to selectively replicate in tumor tissue and to express the immune stimulatory protein GM-CSF . (
  • The essential viral protein EBNA1 is expressed in tumors associated with EBV, during the viral latency processes (but not for latency 0) [ 8 ]. (
  • The Large Tumor antigen (LT) is an early viral protein which has a variety of functions, including manipulation of the cell cycle and initiating viral DNA replication. (
  • Tumor necrosis factor (TNF) receptor 6 (TR6), also called decoy receptor 3 (DcR3) or M68, is a member of the TNF receptor family that is produced as a secreted protein ( 3 , 25 , 35 ). (
  • New binding target for oncogenic viral protein ( The DNA tumor virus simian virus 40 pro. (
  • In a study published in the Journal of Biological Chemistry, researchers at the Fred Hutchinson Cancer Research Center report the discovery of an additional target for T antigen--a protein called Fbw7. (
  • Towards the standardization of tumor diagnosis [abstract]. (
  • Recombinant poxviruses expressing tumor associated antigens (TAAs) are evaluated since 20 years as immunogenic vaccine vector in clinical trials. (
  • It is now proven that tumor-specific antigens exist and that patients mount spontaneous T cell responses against such antigens. (
  • In cancer patients, about one half of the highly tumor-specific antigens recognized by spontaneous T cell responses are encoded by mutated genes, the other half being encoded by cancer-germline genes. (
  • Tumors thrive in an immunosuppressive microenvironment that impedes antitumor innate and adaptive immune responses. (
  • PVSRIPO's immune adjuvancy stimulates canonical innate anti-pathogen inflammatory responses within the tumor microenvironment that culminate in dendritic cell and T cell infiltration. (
  • Our findings provide mechanistic evidence that PVSRIPO functions as a potent intratumor immune adjuvant that generates tumor antigen-specific cytotoxic T lymphocyte responses. (
  • Important to the process of rational vaccine development, monitoring of antigen-specific T-cell responses helps guiding vaccine optimization. (
  • Interestingly, most of the Melan-A-specific T-cell responses identified in advanced tumor-bearing patients focus on the region spanning residues 20 to 40. (
  • Both antibody and cellular responses specific for the tumor antigen 5T4 and the viral vector were monitored throughout the study. (
  • Several tumor-associated antigens have been engineered into vaccinia virus vectors [including modified vaccinia Ankara (MVA)] and the recombinant vaccines shown to induce tumor-associated antigen-specific immune responses in cancer patients ( 9 - 11 ). (
  • Clec9A-TNE encapsulating OVA antigen targeted and activated cross-presenting DCs without additional adjuvant, promoting antigen-specific CD4+ and CD8+ T cell proliferation and CTL and antibody responses. (
  • The paradoxical coexistence of spontaneous tumor antigen-specific immune responses with progressive disease in cancer patients furthers the need to dissect the molecular pathways involved in tumor-induced T cell dysfunction. (
  • Understanding the failure of spontaneous NY-ESO-1-specific T cell responses to promote regression of NY-ESO-1 + tumors is therefore critical for the design of novel therapeutic interventions aimed at overcoming tumor-induced immune escape. (
  • Data accumulated over the past several years have indicated that tumors with spontaneous antitumor T cell responses have high expression of immune-inhibitory pathways that subvert the effector phase of the response. (
  • In healthy individuals, potent EBV-specific CD8+ and CD4+ T-cell responses against a range of viral antigens exert control over long-term infection ( 4 ). (
  • Our results demonstrate that peptide-pulsed DC were efficient in generating CTL responses specific for various viral and tumor epitopes. (
  • Furthermore, IL-7 and IL-10 potentiated the ability of the peptide-pulsed DC to trigger antigen-specific CTL responses. (
  • Immunologic tolerance to endogenous antigens reduces antitumor responses. (
  • We found that tumors grew in all gp70-sufficient mice, while approximately half of gp70-deficient mice controlled tumor growth with endogenous T cell responses. (
  • Although the endogenous T cell responses to TAAs are typically weak and less amenable to experimentation [ 17 ] tumor model systems that employ the endogenous T cell repertoire and natural TAAs may provide more relevant results to guide the design of tumor immunotherapies. (
  • No radiologic tumor responses were observed. (
  • The ability of the two candidate vaccines to generate antigen-specific cellular and humoral responses, respectively, was studied. (
  • The T cell receptor (TCR) repertoires of cytotoxic responses to the immunodominant and subdominant HLA A11-restricted epitopes in the Epstein-Barr virus (EBV) nuclear antigen-4 were investigated in four healthy virus carriers. (
  • Growth delays were monitored by tumor measurements and histological responses were evaluated by immunohistochemistry. (
  • The earliest vaccines, which were developed in 1994-95, tested non-mutated, shared tumor associated antigens that had been shown to be immunogenic and capable of inducing clinical responses in a minority of people with late stage cancer. (
  • These results show that optimized DCs are able to induce MCV-antigen-specific T-cell responses. (
  • Here we show that the complete development of protective CD8+ T cell responses requires prolonged antigen presentation. (
  • The requirement for antigen in the full development of effector and memory responses in different microbial systems is an area of controversy. (
  • However, not all data suggests short exposures to antigen are optimal for T cell responses. (
  • T-cell responses play a central role in the natural history and pathogenesis of viral hepatitis and hepatocellular carcinoma. (
  • Indeed, while spontaneous clearance of hepatitis B and hepatitis C virus infection is associated with an early and vigorous virus specific CD4 and CD8 T-cell response, viral persistence is characterized by the presence of functionally impaired immune responses. (
  • MSC pulsed with peptides from viral antigens evoked interferon (IFN)-gamma and Granzyme B secretion in specific cytotoxic T lymphocytes (CTL) and were lysed, although with low efficiency. (
  • In other instances, the normal peptide is presented at the cell surface and consequently the T lymphocytes that recognize the antigen have been eliminated by the central tolerance process that occurs in the thymus. (
  • In addition, HLA A2-restricted tumor-specific phosphopeptides are immunogenic, and cytotoxic T lymphocytes (CTLs) that distinguish between phosphorylated and native peptides can be generated in HLA A2 transgenic mice ( , 9 ). (
  • Although the presence of tumor-infiltrating lymphocytes (TILs) indicates an endogenous antitumor response, immune regulatory pathways can subvert the effector phase and enable tumor escape. (
  • Researchers took these tumor-infiltrating lymphocytes (TILs) and grew billions of them to re-infuse in her blood, creating an army of immune fighters. (
  • Herein, we demonstrate the impact of immunogenic viral antigens on anti-tumor response and immune editing in MOC2-E6E7, a syngeneic murine oral cancer cell line expressing HPV-16 E6 and E7 oncoproteins. (
  • Thus, viral vectors expressing ICP47 confirmed a diminished TAP-dependant processing of endogenous class-I restricted epitopes while the immunogenic potential of recombinant epitopes directly targeted to the ER was enhanced. (
  • The delivery system consists of a stealth liposome displaying a cancer-specific targeting peptide, named H1299.3, on its exterior surface and encapsulating H250, an immunogenic human leukocyte antigen class 1 restricted peptide. (
  • Moreover, the clonal fraction necessary to lead to rejection of immunogenic tumor subclones depends on the antigen. (
  • The genes for both the small and the large tumor antigen are encoded in the "early region" of the polyomavirus genome, so named because this region of the genome is expressed early in the infectious process. (
  • Simian virus 40 large tumor antigen requires three core replication origin domains for DNA unwinding and replication in vitro. (
  • Simian virus 40 (SV40) large tumor antigen (T antigen) unwinds DNA containing the SV40 origin of replication. (
  • Collectively, our data highlight the need for both immunogenicity and 'driver' status of target antigens to be considered in cancer vaccine design. (
  • Vaccine development in the post-genomic era often begins with the in silico screening of genome information, with the most probable protective antigens being predicted rather than requiring causative microorganisms to be grown. (
  • Metastatic melanoma is however the best studied tumor type in terms of immune reactivity and experimental vaccine testing ( 6 ). (
  • In addition to the tumor-associated antigen, the antigen delivery system is equally as important for the development of a successful cancer vaccine. (
  • For a cancer vaccine to be successful, it must stimulate a potent immune response specific for the target antigen. (
  • The authors examine the basic issues that affect all vaccines (such as immune adjuvants and prime-boost strategies), describe cutting-edge methods for antigen discovery, and review the preclinical development phases for each major vaccine strategy. (
  • This enhances the anti-tumor immune response to tumor antigens released following viral lysis and provides a patient-specific vaccine. (
  • They identify antigens - distinctive targets - on tumors, combine them with substances (adjuvants) to enhance immune response, and then inject the vaccine to treat a given cancer. (
  • Established subcutaneous Renca-MUC1 tumors were treated with 8 Gy radiation on day 11 and peritumoral injections of MVA-MUC1-IL2 vector on day 12 and 17, or using a reverse sequence of vaccine followed by radiation. (
  • Tumor growth delays observed by tumor irradiation combined with MVA-MUC1-IL-2 vaccine were significantly more prolonged than those observed by vaccine, radiation, or radiation with MVA empty vector. (
  • An abscopal effect was measured by rejection of an untreated tumor on the contralateral flank to the tumor treated with radiation and vaccine. (
  • STag is expressed early in the infectious cycle and is usually not essential for viral proliferation, though in most polyomaviruses it does improve replication efficiency. (
  • Because polyomavirus genome replication relies on the DNA replication machinery of the host cell, the cell must be in S phase (the part of the cell cycle in which the host cell's genome is normally replicated) in order to provide the necessary molecular machinery for viral DNA replication. (
  • The polyomavirus tumor (T) antigens play crucial roles in viral replication, transcription, and cellular transformation. (
  • Viral RNA was detected by reverse transcription-polymerase chain reaction in lung, intestine, and spleen tissues, but positive-stranded viral RNA indicating virus replication was confined to the lung and intestine. (
  • In contrast to disseminated infection documented in other mammals and birds, H5N1 viral replication in humans may be restricted to the lung and intestine, and the major site of H5N1 viral replication in the lung is the pneumocyte. (
  • Despite severe and generalized clinical manifestations, the result of multiple organ dysfunction, previous limited autopsy data failed to show evidence of viral replication beyond the respiratory tract ( 10 , 11 ). (
  • The origin requirement for unwinding can be satisfied by the 64-base-pair SV40 core origin that supports T-antigen-dependent DNA replication both in vivo and in vitro. (
  • Simian virus 40 large T antigen can specifically unwind the central palindrome at the origin of DNA replication. (
  • In vivo replication assays confirm that phosphorylation of T271 does not play a role in viral replication, while modification at T297 and T299 have dramatic and opposing effects on LT's ability to initiate replication from the viral origin. (
  • These studies provide a framework for understanding how phosphorylation of LT may dynamically regulate viral replication. (
  • Diaz J, Wang X, Tsang SH, Jiao J, You J. Phosphorylation of Large T Antigen Regulates Merkel Cell Polyomavirus Replication. (
  • DNA tumor viruses proliferate by hijacking their host cell's DNA replication machinery. (
  • Drs. Clurman and Welcker suspect that by acting as a decoy and binding to Fbw7, T antigen protects cellular Fbw7 targets that facilitate viral replication and tumorigenesis. (
  • Some of this control of host replication is through the interaction of the C‐terminal half (residues 351-626) of SV40 large T antigen with the p53 tumor suppressor ( Kierstead and Tevethia, 1993 ). (
  • Mutated genes contribute greatly to the immunogenicity of human tumors. (
  • The contribution of these antigens to tumor immunogenicity is expected to vary according to the mutation rate: higher in lung carcinomas arising in tobacco smokers, in melanomas owing to mutations induced by UV and in the 15% of colorectal carcinomas that have hypermutated DNA owing to defects in the DNA mismatch repair pathway. (
  • Reciprocal relationship between normal transplantation antigens (H-2) and tumor-specific immunogenicity. (
  • To understand the determinants of MHC-I peptide immunogenicity in nascent tumors, we tested the ability of thousands of MHC-I ligands to cause tumor subclone rejection in immunocompetent mice by use of a new 'PresentER' antigen presentation platform. (
  • Using orthotopic syngeneic models, we observed in vivo tumor growth kinetics of MOC2-E6E7 is delayed in immunocompetent mice compared to parental MOC2 tumors. (
  • In other cases, the antigen expressed during in vivo infection is not expressed during in vitro cultivation. (
  • Administration of anti-LAG-3 plus anti-4-1BB mAbs was therapeutic against tumors in vivo, which correlated with phenotypic normalization. (
  • These vectors selectively targeted DCs in vitro and in vivo resulting in vector-mediated antigen expression and efficient maturation of DCs. (
  • An antigen is said to be protective if it is able to induce protection from subsequent challenge by a disease-causing infective agent in an appropriate animal model following immunization. (
  • Fey, E. G., and Penman, S., 1984, Tumor promoters induce a specific morphological signature in the nuclear matrix-intermediate filament scaffold of Madin Darby canine kidney (MDCK) cell colonies, Proc. (
  • Much of the work done dissecting CD8 + T cell dysfunction in the tumor microenvironment has been translated from chronic infection examples, such as the chronic LCMV mouse model ( Pauken and Wherry, 2015 ). (
  • We did not detect viral RNA in urine (Ap- of the infection ranged from mild influenza-like illness to pendix Table 3). (
  • Tumor-specific criteria are generally more useful than infection-based criteria. (
  • The specific infection of NMuMG-T-derived tumours was verified by the lack of viral DNA in kidney, lung or spleen although low levels of viral DNA was occasionally found in liver. (
  • The vaccination site increasingly resembles a viral infection, with lots of damaged normal tissue and antigens," Overwijk says. (
  • Treatments that cure bacterial infections are not useful in the treatment of viral infection. (
  • HBV Infection occurs mainly in the liver, but viral antigens can be detected in the blood throughout the body. (
  • Chronic Infection is indicated by the presence of viral antigens in the blood for longer than 6 months. (
  • Viral integration into the host genome is regularly found in chronic liver infection and cancer. (
  • CAR-T cell therapies such as Gilead Sciences' Yescarta and Novartis' Kymriah have been proven useful against B-cell blood cancers, but the technology has been difficult to translate to solid tumors. (
  • The exact molecular mechanism of T cell exhaustion has been a mystery, but scientists believe it partially explains why CAR-Ts can't act on solid tumors. (
  • Human leukocyte antigen (HLA) class I molecules present a variety of posttranslationally modified epitopes at the cell surface, although the consequences of such presentation remain largely unclear. (
  • Thus, comparison of the memory response to two epitopes derived from the same viral antigen and presented through the same MHC class I allele suggests that immunodominance may correlate with the capacity to maintain a broad TCR repertoire. (
  • Natural killer (NK) cell recognition of phosphoantigens has also revealed that phosphorylation of human leukocyte antigen (HLA) Cw4-bound peptide antigens reduced inhibitory signals mediated via killer Ig receptors and led to enhanced NK cell cytolysis ( , 4 ). (
  • Cellular transformation by Simian Virus 40 and Murine Polyoma Virus T antigens. (
  • Simian Virus 40 (SV40) and Mouse Polyoma Virus (PY) are small DNA tumor viruses that have been used extensively to study cellular transformation. (
  • The SV40 early region encodes three tumor antigens, large T (LT), small T (ST) and 17KT that contribute to cellular transformation. (
  • The unique contributions of SV40 LT and ST and PY MT to cellular transformation have provided significant insights into our understanding of tumor suppressors, oncogenes and the process of oncogenesis. (
  • They bind viral ligands such as hemagglutinins and hemagglutinin neuraminidases, some bacterial ligands and cellular ligands related with tumour growth such as PCNA . (
  • Moreover, EBNA1 could interact with the cellular and viral promoters, regulating the gene transcription level [ 9 ]. (
  • The study of DNA tumors viruses has been an extremely important tool in understanding the cellular pathways that regulate cell division and are disrupted in cancer. (
  • Unlike class Ia HLA molecules, class Ib HLA-E, -F, and -G antigens display very limited or no polymorphism within the human population, may function in presenting limited sets of peptides, and/or exhibit a restricted tissue expression ( 2 ). (
  • MSC transfected with tumor mRNA or infected with a viral vector carrying the Hepatitis C virus NS3Ag gene induced cytokine release but were not killed by specific CTL, even following pretreatment with IFN-gamma. (
  • The LTag gene is usually encoded in two exons, of which the first overlaps with the gene for STag (and sometimes other tumor antigens as well, such as the murine polyomavirus middle tumor antigen). (
  • The Melan-A gene encodes a 118 amino acid long polypeptide expressed by normal melanocytes and the majority of primary and metastatic tumors ( 7 ). (
  • The Fbw7 gene is located in a chromosomal region that is deleted in up to 30% of human tumors. (
  • 9. The method of anyone of claims 1 - 3 , wherein the gene encodes an antigen. (
  • EBV-mediated carcinogenesis is most likely caused by the actions of viral gene products. (
  • Fully human antibodies against a specific antigen can be prepared by administering the antigen to a transgenic animal which has been modified to produce such antibodies in response to antigenic challenge, but whose endogenous loci have been disabled. (
  • These are known as antigen-armed antibodies (AgAbs). (
  • We are currently evaluating the efficacy of this therapeutic approach in a mouse model of B cell lymphoma (A20) using antibodies that recognize murine B cell markers and that are loaded with antigens specific for mouse cytomegalovirus. (
  • AgAb consist of antibodies specific to CD19, CD20, CD21 and CD22 that are fused to antigens from the Epstein-Barr virus. (
  • Their high specificity results from the use of antibodies and purified antigens as reagents. (
  • Qualitative immunoassays are often used to detect antigens on infectious agents and antibodies that the body produces to fight them. (
  • Immunoassays for antibodies produced in viral hepatitis, HIV , and Lyme disease are commonly used to identify patients with these diseases. (
  • By linking several antibodies to the particle, the particle is able to bind many antigen molecules simultaneously. (
  • In addition, prophylactic and, most likely, also therapeutic vaccination against tumors will save millions from metastatic disease. (
  • Vaccination against viral infections has saved millions of lives by protecting many individuals from diseases such as measles, rubella, mumps, and polio. (
  • Likewise, novel approaches for vaccination against tumors which counteract the immunosuppression associated with cancer are needed ( 3 ). (
  • Characterization of T Antigens, Including Middle T and Alternative T, Expressed by the Human Polyomavirus Associated with Trichodysplasia Spinulosa. (
  • Asymmetric assembly of Merkel cell polyomavirus large T-antigen origin binding domains at the viral origin. (
  • Merkel cell carcinoma (MCC) is a rare but very aggressive skin tumor that develops after integration of a truncated form of the large T-antigen (truncLT) of the Merkel cell polyomavirus (MCV) into the host's genome. (
  • Large (LT), 17KT and Small (ST) of SV40 and PY as well as Middle (MT) T antigens from PY share coding regions. (
  • The N terminal 82 (SV40) and 79 (PY) residues for all T antigens are identical (magenta). (
  • In SV40 and JC virus, STag is not required for viral proliferation, but does improve efficiency. (
  • This antigen is from the simian vacuolating virus 40 (SV40). (
  • Large T antigens play a role in regulating the viral life cycle of the polyomaviridae viruses, such as SV40. (
  • The SV40 large T-antigen origin binding domain directly participates in DNA unwinding. (
  • Simian virus 40 (SV40) accomplishes this task by producing the highly oncogenic large T antigen. (
  • Inactivation of the retinoblastoma (Rb) tumor suppressor by Simian virus 40 (SV40) large T antigen is one of the central features of tumorigenesis induced by SV40. (
  • The crystal structure of the N‐terminal region (residues 7-117) of SV40 large T antigen bound to the pocket domain of Rb reveals that large T antigen contains a four‐helix bundle, and residues from helices α2 and α4 and from a loop containing the LxCxE motif participate in the interactions with Rb. (
  • The DNA tumor virus simian virus 40 produces the Large T antigen which. (
  • Tumor biomarkers act as important contextual cues or signals of cancer status. (
  • By real-time PCR, we detected downregulation of E6 and E7 genes in MOC2-E6E7 tumors only in immunocompetent mice, suggesting the loss of ectopic viral antigen expression due to immune editing. (
  • Cancer-germline genes are an important source of tumor-specific antigens. (
  • These genes are expressed in a significant fraction of tumors of many different histological types. (
  • 27 Nodal and splenic MZLs share recurrent mutations affecting the Notch pathway and the transcription factor KLF2, but differ for the inactivation of 2 tumor-suppressor genes, detected exclusively ( PTPRD ) or much more commonly ( KMT2D/MLL2 ) in the nodal type. (
  • The available reverse genetics systems allow for insertion of additional genes, including heterologous antigens. (
  • To investigate the mechanisms involved in MSC resistance to CTL-mediated lysis, we analyzed expression of human leukocyte antigen (HLA) class I-related antigen-processing machinery (APM) components and of immunosuppressive HLA-G molecules in MSC. (
  • antigen-antibody reaction the reversible binding of antigen to homologous antibody by the formation of weak bonds between antigenic determinants on antigen molecules and antigen binding sites on immunoglobulin molecules. (
  • Furthermore, using a novel antigen presentation system, we observed that the induction of mitophagy by TNF-α enabled the processing and presentation of mitochondrial antigens at the cell surface by MHC class I molecules. (
  • Three murine mammary tumor virus (MuMTV)-producing epithelial cell lines derived from murine mammary tumors were examined in order to identify the MuMTV-specific cell surface antigens and their distribution on the cell surface, to study the kinetics of the MuMTV envelope precursor processing, virus assembly, and release, and to characterize the soluble MuMTV antigens that are shed into culture medium. (
  • The attenuated strain of vaccinia virus, modified vaccinia Ankara (MVA) encoding the tumor antigen 5T4 (TroVax), has been evaluated in an open-label phase II study in metastatic colorectal cancer patients. (
  • Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. (
  • Although antigen-anti-Clec9A mAb conjugates target cross-presenting DCs, adjuvant must be codelivered for cytotoxic T lymphocyte (CTL) induction. (
  • 19. An antibody of fragment thereof according to claim 17 , wherein the antibody or fragment thereof has no effect on the induction of tumor fibrin deposition. (
  • Specific carcinoembryonic antigens of the human digestive system. (
  • The detection of carcinoembryonic antigen in whole serum from patients with malignant and nonmalignant disease. (
  • carcinoembryonic antigen (CEA) an oncofetal glycoprotein antigen originally thought to be specific for adenocarcinoma of the colon, but now known to be found in many other cancers and some nonmalignant conditions. (
  • [6] numerous experiments have demonstrated their ability to readily adjust to the immediate environment and formulate antigen-specific immunological memory , fundamental for responding to secondary infections with the same antigen. (
  • Modular Three-component Delivery System Facilitates HLA Class I Antigen Presentation and CD8(+) T-cell Activation Against Tumors. (
  • Treatment with this liposome results in a significant reduction of tumor growth using an aggressive LLC1 model in vaccinated C57BL/6 mice. (
  • Antigenic properties of methylcholanthrene-induced tumors in mice of the strain of origin. (
  • Injection of HAdV-2 into tumours established by NMuMG-T in SCID mice caused reduced tumour growth and signs of intratumoural lesions. (
  • Of particular note were experiments showing that the cancer susceptibility of immunocompetent mice (to both spontaneous and carcinogen-induced tumors) was similar to that of nude mice that had major but not total immunodeficiency ( 5 , 6 ). (
  • Subunit vaccines contain one or more pure or semi-pure antigens. (
  • Vaccines can not be developed using this approach for microorganisms which can not easily be cultured and only allows for the identification of those antigens which can be obtained in sufficient quantities. (
  • These findings provide insights into the mode of phosphopeptide presentation by HLA as well as providing a platform for the rational design of a generation of posttranslationally modified tumor vaccines. (
  • Potentially tumour-causing in primates and humans, it is used in laboratory research and in vaccines. (
  • For years, scientists have crafted vaccines designed to treat cancer, rather than to prevent it, by priming the immune system to track down and kill tumors. (
  • Technological developments in the past few years have enabled the investigation of vaccines that target mutated antigens that are patient specific. (
  • The p53 tumor suppressor binds to the Helicase domain and requires residue 350 through 627. (
  • In the Journal of Biological Chemistry paper, Dr. Welcker and Dr. Bruce Clurman report that T antigen also binds to another tumor suppressor, Fbw7. (
  • In studying the immunopathogenesis of herpes-associated erythema multiforme, we examined skin lesions for the presence of a herpes simplex viral antigen by an indirect immunofluorescence test using a monoclonal antibody to a major type-common glycoprotein antigen, gB. (
  • Virologic diagnosis was made by antigen detection, viral culture, and reverse transcription-polymerase chain reaction (RT-PCR) on a nasopharyngeal wash specimen as described ( 12 ) and was confirmed by seroconversion of neutralizing antibody against H5N1 virus. (
  • Immunoassays measure the formation of antibody-antigen complexes and detect them via an indicator reaction. (
  • The simplest immunoassay method measures the quantity of precipitate, which forms after the reagent antibody (precipitin) has incubated with the sample and reacted with its respective antigen to form an insoluble aggregate. (
  • The immediate union of antibody and antigen forms immune complexes that are too small to precipitate. (
  • Radioimmunoassay (RIA) is a method employing radioactive isotopes to label either the antigen or antibody. (
  • These methods use an enzyme to label either the antibody or antigen. (
  • 1. one that combines with antibody produced in response to a different but related antigen, owing to similarity of antigenic determinants. (
  • 2. identical antigens in two bacterial strains, so that antibody produced against one strain will react with the other. (
  • DNA tumor viruses proliferate by hijacking their host cell's DNA repli. (
  • Some of the earliest work on the identification of oncogenes and tumor suppressors utilized viruses. (
  • This occurs because each T cell is endowed with a highly specific receptor that can bind to an antigen present at the surface of another cell. (
  • To study the intrinsic link between the deregulated signaling cascade present in many cancers and the ability of antigen processing to alert CTLs to such molecular events, we have investigated the structural and biophysical properties and structures of 3 HLA A2 phosphopeptide complexes derived from cell division cycle (CDC) 25b, β-catenin, and insulin receptor substrate (IRS) 2 and have compared them with the structures of their nonphosphorylated counterparts. (
  • Among the numerous antigens expressed by cutaneous melanoma, Melan-A/Mart-1 (hereafter Melan-A) is one of the best characterized thus far. (
  • Collectively, our findings support the use of Tim-3-Tim-3L blockade together with PD-1-PD-L1 blockade to reverse tumor-induced T cell exhaustion/dysfunction in patients with advanced melanoma. (
  • Among these antigens, cancer-germline antigens (CGAs) are expressed by tumors of many different histological types, including melanoma, but not by normal tissues, except testis. (
  • Carrel S, Theilkaes L. Evidence for a tumour-associated antigen in human malignant melanoma. (
  • Interim results from a phase III trial of talimogene laherparepvec in melanoma showed a significant tumour response compared to administration of GM-CSF alone. (
  • Tumor necrosis factor-α mRNA was seen in lung tissue. (
  • The present invention relates to ligands which bind to human tumor necrosis factor alpha (TNF) in a manner such that upon binding of these ligands to TNF the biological activity of TNF is modified. (
  • Furthermore, it has been suggested that EBNA1 would be necessary the tumor cell proliferation [ 14 ]. (
  • Adoptive cell transfer (ACT) of antigen (Ag)-specific CTLs is a promising treatment for a variety of malignancies ( 1 ). (
  • There is an urgent need to find a new approach to generate tumor-reactive CTLs for successful ACT-based therapies. (
  • In this study we present evidence suggesting that the tumor promoter 12-0-tetradecanoyl phorbol 13-acetate (TPA) induces a specific alteration in the morphology and cytoskeletal organization of differentiated epithelial cell colonies. (
  • Elevated levels are seen in association with epithelial ovarian carcinomas, particularly nonmucinous tumors, as well as with some other malignancies, various benign pelvic disorders, tuberculosis, and cirrhosis. (
  • In conclusion, human MSC can process and present HLA class I-restricted viral or tumor antigens to specific CTL with a limited efficiency, likely because of some defects in APM components. (
  • Genetic processes other than point mutations can lead to tumor-specific antigens. (
  • In addition, the phosphoamino acid stabilized the HLA peptide complex in an epitope-specific manner and was observed to exhibit discrete flexibility within the antigen-binding cleft. (
  • Non-antigen-specific stimulatory cancer immunotherapies are commonly complicated by off-target effects. (
  • We also observed that PD-1 regulates NY-ESO-1-specific CD8 + T cell expansion upon chronic antigen stimulation. (
  • A more detailed study has been hampered by a lack of cell surface markers defining tumor-specific dysfunctional TILs, and PD-1 alone is not sufficient. (
  • Tumour-specific antigen related to rat histocompatibility antigens. (
  • Tissue-specific antigens. (
  • NAIRN RC, GHOSE T, FOTHERGILL JE, McENTEGART MG. Kidney specific antigen and its species distribution. (
  • The natural history of specific viral types may be different. (
  • Each TCR has a unique binding site that can attach to a specific portion of the antigen called the epitope. (
  • Since the introduction of the prostate-specific antigen (PSA) test in 1987, the incidence rates of prostate cancer have seen an increase, likely due to earlier detection. (
  • The human oncofetal antigen 5T4 is a 72-kDa leucine-rich membrane glycoprotein which is expressed at high levels on the placenta and also on a wide range of human carcinomas including colorectal, gastric, renal, and ovarian cancers but rarely on normal tissues ( 2 - 4 ). (
  • The human oncofetal antigen 5T4 is a 72-kDa membrane glycoprotein that is expressed at high levels on the placenta and also on a wide range of human carcinomas, including colorectal, renal, gastric, and ovarian ( 1 - 3 ). (
  • A large glycoprotein of molecular weight ~210 kD, CA 19-9 is a cell surface antigen located on MUC-1 whose carbohydrate determinant is defined as a sialylated Lewis (a) blood group antigen. (
  • cancer antigen 125 (CA 125) a glycoprotein antigen found in normal adult tissues such as the epithelium of the fallopian tubes, the endometrium, the endocervix, the pleura, and the peritoneum. (
  • In oncogenic polyomaviruses, the tumor antigens are responsible for the transformation activity, although the exact molecular mechanisms vary from one virus to another. (
  • A blood test to watch breast cancer's 'molecular clock' could help track the growth of multiple tumors around the body and monitor how they are responding to treatment, new research suggests. (
  • The functional properties of phagosomes appeared relatively recently in the evolution of multicellular organisms through the acquisition of molecular machineries that transformed phagosomes from lytic vacuoles into organelles fully competent for antigen presentation ( 2 ). (
  • The two central helices and a connecting loop in large T antigen have structural similarities with the J domains of the molecular chaperones DnaJ and HDJ‐1, suggesting that large T antigen may use a chaperone mechanism for its biological function. (
  • However, there are significant differences between large T antigen and the molecular chaperones in other regions and these differences are likely to provide the specificity needed for large T antigen to inactivate Rb. (