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. ...
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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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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 - ...
SV40 and/or DNA sequences indistinguishable from SV40 have been detected in several types of human tumours. The oncoprotein of Simian virus 40, SV40 large T-antigen (Tag), is known to bind and inactivate tumour suppressor proteins, such as members of the retinoblastoma family and p53, thereby promot …
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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We previously analyzed human embryonic kidney (HEK) cell lines for the effects that simian virus 40 (SV40) small tumor antigen (ST) has on gene expression using Affymetrix U133 GeneChips. To cross-validate and extend our initial findings, we sought to compare the expression profiles of these cell lines using an alternative microarray platform. METHODS: We have analyzed matched cell lines with and without expression of SV40 ST using an Applied Biosystems (AB) microarray platform that uses single 60-mer oligonucleotides and single-color quantitative chemiluminescence for detection. RESULTS: While we were able to previously identify only 456 genes affected by ST with the Affymetrix platform, we identified 1927 individual genes with the AB platform. Additional technical replicates increased the number of identified genes to 3478 genes and confirmed the changes in 278 (61%) of our original set of 456 genes. Among the 3200 genes newly identified as affected by SV40 ST, we confirmed 20 by QRTPCR including
In this report we present evidence that simian virus 40 T antigen encodes a biological activity that is functionally equivalent to the transforming activity lost by deletion of the E1A p300-binding region. T-antigen constructs from which the pRb-binding region has been deleted are virtually unable to induce foci of transformed cells in a ras cooperation assay in primary baby rat kidney cells. Nevertheless, such a construct can cooperate with an E1A N-terminal deletion mutant, itself devoid of transforming activity, to induce foci in this assay. The heterologous trans-cooperating activity observed between E1A and T-antigen deletion products is as efficient as trans cooperation between mutants expressing individual E1A domains. The cooperating function can be impaired by a deletion near the N terminus of T antigen. Such a deletion impairs neither the p53-binding function nor the activity of the pRb-binding region.. ...
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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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 ...
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tumors in dogs." This is not true. Vaccine associated sarcomas have been documented in dogs. Fibrosarcomas at presumed sites of ... Veterinarians stress the importance of vaccinating against the fatal viral disease because of its continued presence in Maine. ... The average cat by twelve years of age, with the prevailing recommendations would receive 107 antigens. With the ... "Now he has two more tumors. It may be in his lymph glands." Officials have shown a degree of sympathy. This week, Dr. Robert ...
tumors in dogs." This is not true. Vaccine associated sarcomas have been documented in dogs. Fibrosarcomas at presumed sites of ... Veterinarians stress the importance of vaccinating against the fatal viral disease because of its continued presence in Maine. ... The average cat by twelve years of age, with the prevailing recommendations would receive 107 antigens. With the ... "Now he has two more tumors. It may be in his lymph glands." Officials have shown a degree of sympathy. This week, Dr. Robert ...
tumors in dogs." This is not true. Vaccine associated sarcomas have been documented in dogs. Fibrosarcomas at presumed sites of ... Veterinarians stress the importance of vaccinating against the fatal viral disease because of its continued presence in Maine. ... The average cat by twelve years of age, with the prevailing recommendations would receive 107 antigens. With the ... "Now he has two more tumors. It may be in his lymph glands." Officials have shown a degree of sympathy. This week, Dr. Robert ...
tumors in dogs." This is not true. Vaccine associated sarcomas have been documented in dogs. Fibrosarcomas at presumed sites of ... Veterinarians stress the importance of vaccinating against the fatal viral disease because of its continued presence in Maine. ... The average cat by twelve years of age, with the prevailing recommendations would receive 107 antigens. With the ... "Now he has two more tumors. It may be in his lymph glands." Officials have shown a degree of sympathy. This week, Dr. Robert ...
Melanoma Antigen. *Microtubule-Associated Protein. *Myelin Oligodendrocyte GlycoP. *Myoglobin. *Myosin Light Chain ...
  • Immunotherapeutic treatments in head and neck cancer clinical trials include cancer vaccines targeting foreign viral antigens or mutational neoantigens derived from cancer-expressed proteins. (
  • 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. (
  • 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. (
  • It was developed to allow antigen classification solely based on the physicochemical properties of proteins without recourse to sequence alignment. (
  • tumour cell lines and proteins obtained. (
  • Antigenic peptides derived from the encoded proteins are therefore presented on the surface of tumor cells and not on normal cells. (
  • 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). (
  • 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. (
  • 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. (
  • Finally, most tumor-associated antigens (TAAs) are derived from non-mutated self proteins, resulting in deletion of CTL with high avidity for TAAs. (
  • Deficiencies or abnormalities in these proteins may lead to unregulated cell growth and tumor development. (
  • 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. (
  • 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. (
  • 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. (
  • They spot their target by identifying small pieces of proteins - or antigens - at the surface of diseased cells. (
  • latent membrane proteins (LMP's) and EBV nuclear antigen (EBNA's). (
  • To accomplish that, tumor cells may be infected with various types of viruses so that viral proteins are expressed on the surface, and transduced with genes expressing cytokines such as IL-2 and GM-CSF, or genes for HLA molecules or co-stimulatory molecules. (
  • 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. (
  • Antigen-specific immunotherapy, combining viral tumor antigen or personalized neoepitopes with immune targeting, offers a solution. (
  • 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. (
  • 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. (
  • 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. (
  • 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. (
  • They are also considered a form of specific immunotherapy because they attempt to stimulate an immune response that can directly target the tumor antigens, in contrast to non-specific approaches such as cytokines that broadly stimulate the immune system. (
  • During the process of cross-presentation, viral or tumor-derived antigens are presented to CD8 + T cells by Batf3- dependent CD8α + /XCR1 + classical dendritic cells (cDC1s). (
  • However, similar to Batf3 -/- mice, Wdfy4 -/- mice failed to prime virus-specific CD8 + T cells in vivo or induce tumor rejection, revealing a critical role for cross-presentation in antiviral and antitumor immunity. (
  • 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. (
  • The programmed death receptor 1 (PD-1) pathway is an immune checkpoint inhibitor exploited by tumor cells to suppress antitumor immunity. (
  • 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. (
  • With the availability of sensitive methods, naturally occurring T cells directed against tumor-associated antigens (TAAs) can be frequently detected in cancer patients. (
  • The possible role of TAA-specific T cells in immunosurveillance and tumor escape and the implications for immunological treatment strategies are discussed. (
  • Naturally occurring T cells against TAAs are a common phenomenon in tumor patients. (
  • Some investigators have performed in vitro restimulation of lymphocytes to increase the frequency of antigen-specific T cells. (
  • 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. (
  • 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 ). (
  • 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. (
  • 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. (
  • 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. (
  • 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. (
  • Knowing if therapeutic strategies have worked will likely require measurement of immune-response molecules, rather than genetic analysis of tumor cells. (
  • Here we developed a CRISPR-Cas9 genome-targeting system that does not require viral vectors, allowing rapid and efficient insertion of large DNA sequences (greater than one kilobase) at specific sites in the genomes of primary human T cells, while preserving cell viability and function. (
  • Second, we replaced the endogenous T cell receptor ( TCR ) locus with a new TCR that redirected T cells to a cancer antigen. (
  • The resulting TCR-engineered T cells specifically recognized tumour antigens and mounted productive anti-tumour cell responses in vitro and in vivo. (
  • Together, these studies provide preclinical evidence that non-viral genome targeting can enable rapid and flexible experimental manipulation and therapeutic engineering of primary human immune cells. (
  • Fig. 1: Efficient non-viral genome targeting in primary human T cells. (
  • Homology-directed recombination for enhanced engineering of chimeric antigen receptor T cells. (
  • 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. (
  • Expression and disposition of the murine mammary tumor virus (MuMTV) envelope gene products by murine mammary tumor cells. (
  • 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. (
  • The absence of detectable viral mented in other mammals and birds, H5N1 viral replication antigen-positive cells in previous reports may relate to the in humans may be restricted to the lung and intestine, and fact that the patients died during the late phase of the dis- the major site of H5N1 viral replication in the lung is the pneumocyte. (
  • However, the lack of flexible systems targeting tumor antigens to cross-presenting dendritic cells (DCs) limits clinical development. (
  • 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. (
  • 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. (
  • 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 ). (
  • 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. (
  • 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. (
  • The purpose of this study is to characterize the molecular and cell biology of the tumor cells in lymphoma. (
  • Focal staining showed this antigen to be present in epidermal cells in 12 of 16 skin biopsy specimens. (
  • 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 ]. (
  • Selection of the appropriate adjuvant to activate antigen-presenting cells to stimulate immune responses, is required. (
  • 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. (
  • 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. (
  • An antibody is a protein (immunoglobulin) produced by B-lymphocytes (immune cells) in response to stimulation by an antigen. (
  • 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. (
  • 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. (
  • 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 . (
  • 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. (
  • 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. (
  • 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 . (
  • 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 ). (
  • 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. (
  • 19) NO has different tasks such as killing infected cells, tumor cells, and parasitic pathogens. (
  • Chronic viral infections often result in ineffective CD8 T-cell responses due to functional exhaustion or physical deletion of virus-specific T cells. (
  • Production of interleukin 2 and the ability to lyse target cells in vitro were the first functions compromised, followed by the ability to make tumor necrosis factor alpha, while gamma interferon production was most resistant to functional exhaustion. (
  • A model is proposed in which antigen levels drive the hierarchical loss of different CD8 T-cell effector functions during chronic infection, leading to distinct stages of functional impairment and eventually to physical deletion of virus-specific T cells. (
  • Further, rhesus macaques infected with simian immunodeficiency virus (SIV) show significantly higher viral loads if CD8 T cells are eliminated by antibody-mediated depletion ( 38 ). (
  • However, in many patients CD8 T cells fail to contain viral replication, particularly during HIV, HBV, and HCV infections. (
  • Recent studies suggest that functional impairment (exhaustion) and/or physical deletion of CD8 T cells can accompany ineffective viral control ( 44 , 85 ). (
  • CD8 T cells are critical for the control of LCMV infection, and the adoptive transfer of memory CD8 T cells into persistently infected mice can lead to viral elimination ( 37 ). (
  • As Dr. Disis explained, tumor cells express specific antigens on the cell surface, usually within the MHC molecules. (
  • The problem with tumor cells is that they cannot stimulate a T cell response by na ve T cells, in part because they lack necessary co-stimulatory molecules. (
  • However, dendritic cells - a type of antigen-presenting cell - can provide them. (
  • The dendritic cell can then present the tumor antigens on their surface within MHC molecules, ready to activate T cells. (
  • Once the T cells are activated, they are capable of recognizing and destroying antigen-expressing tumors. (
  • An interesting approach to detecting a clinical response was used in lymphoma patients, in whom circulating tumor cells could be detected by polymerase chain reaction (PCR) prior to immunization. (
  • In this study, tumor cells could not be detected in peripheral blood of some patients following immunization. (
  • Some studies have used autologous tumor, in which tumor cells are extracted from surgical resection or biopsy specimens. (
  • Tumor cells can also be modified to make them more immunogenic. (
  • The idea is irradiate the cells so they can no longer proliferate, then inject the tumor cells back into the patient. (
  • 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 ). (
  • Pillars Article: IFNγ and Lymphocytes Prevent Primary Tumour Development and Shape Tumour Immunogenicity. (
  • 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. (
  • 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. (
  • Also, antigen processing and presentation to Th1 lymphocytes by macrophages induce cell-mediated immunity. (
  • 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. (
  • 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. (
  • 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. (
  • Recombinant poxviruses expressing tumor associated antigens (TAAs) are evaluated since 20 years as immunogenic vaccine vector in clinical trials. (
  • 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. (
  • It has long been a matter of debate whether tumors are spontaneously immunogenic in patients. (
  • 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. (
  • 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. (
  • Moreover, the clonal fraction necessary to lead to rejection of immunogenic tumor subclones depends on the antigen. (
  • Towards the standardization of tumor diagnosis [abstract]. (
  • This phase I study evaluated the safety, maximum tolerated dose, antitumor activity, and pharmacokinetics and pharmacodynamics of pembrolizumab in patients with advanced solid tumors. (
  • Tumor response was assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. (
  • Pembrolizumab was well tolerated and associated with durable antitumor activity in multiple solid tumors. (
  • This report details the first-in-human experience for pembrolizumab in patients with advanced solid tumors, including in-depth pharmacokinetic and pharmacodynamic analyses. (
  • 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. (
  • Collectively, our data highlight the need for both immunogenicity and 'driver' status of target antigens to be considered in cancer vaccine design. (
  • 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. (
  • We designed a functional CRISPR screen for previously unknown regulators of cross-presentation, and identified the BEACH domain-containing protein WDFY4 as essential for cross-presentation of cell-associated antigens by cDC1s in mice. (
  • 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. (
  • T cell responses against various antigens, including melanoma differentiation antigens, carcinoembryonic antigen, epithelial cell adhesion molecule, her-2/neu, Wilms' tumor protein, proteinase 3, NY-ESO-1, and surviving, have been reported in a substantial number of patients. (
  • 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. (
  • 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 . (
  • 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. (
  • 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. (
  • 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. (
  • Until now, most efforts focused on the identification of virus-specific epitopes, whereas immune responses directed against shared cellular tumor-specific antigens have not been evidenced. (
  • In this study, we measured T-cell responses against viral (n = 3) and tumor antigens (n = 47) from TILs derived from 21 MCC tumors. (
  • Virus-specific CD8 T-cell responses dominated MCC-specific immune responses, and we identified two new HLA-peptide complexes derived from the LT antigen, located in a region encompassing 3 previously identified epitopes. (
  • 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. (
  • In contrast, other TAAs, including most antigens of the MAGE family, do not usually elicit spontaneous T cell responses. (
  • These TAAs have facilitated the analysis of T cell responses to tumors and are promising targets for immunotherapeutic strategies. (
  • 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. (
  • 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. (
  • 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. (
  • 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 ). (
  • 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 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. (
  • These results show that optimized DCs are able to induce MCV-antigen-specific T-cell responses. (
  • The ability of the two candidate vaccines to generate antigen-specific cellular and humoral responses, respectively, was studied. (
  • Indeed, potent human immunodeficiency virus (HIV)-specific CD8 T-cell responses correlate with acute viral control and long-term nonprogression ( 16 , 42 , 55 , 56 , 61 , 66 ). (
  • However, the impact of chronic viral infection on the induction and maintenance of epitope-specific CD8 T-cell responses and the impact of persisting antigen on distinct T-cell effector functions are not well understood. (
  • Despite severe and generalized transcription-polymerase chain reaction in lung, intestine, clinical manifestations, the result of multiple organ dys- and spleen tissues, but positive-stranded viral RNA indicat- function, previous limited autopsy data failed to show evi- ing virus replication was confined to the lung and intestine. (
  • 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. (
  • 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. (
  • 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. (
  • Tumor necrosis factor- mRNA was seen not been clearly established by immunohistochemical 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. (
  • The first defensive line is production and secretion of cytokines such as type i interferon (IFN) and tumor necrosis factor (TNF). (
  • 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. (
  • Metastatic melanoma is however the best studied tumor type in terms of immune reactivity and experimental vaccine testing ( 6 ). (
  • 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. (
  • Interim results from a phase III trial of talimogene laherparepvec in melanoma showed a significant tumour response compared to administration of GM-CSF alone. (
  • Carrel S, Theilkaes L. Evidence for a tumour-associated antigen in human malignant melanoma. (
  • Allogeneic cell lines have also been developed for tumors such as melanoma that likely encompass many of the tumor-associated antigens expressed by the melanomas of most affected individuals. (
  • 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. (
  • 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. (
  • 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 ). (
  • Activation is dependent on the targeting peptide, previous antigen exposure, and utilizes a novel autophagy-mediated mechanism to facilitate presentation. (
  • 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. (
  • Immunomedics, Inc., a biopharmaceutical company focused on developing monoclonal antibodies to treat cancer and other serious diseases, today reported that TF2, a proprietary bispecific antibody, has shown selective tumor localization and minimal normal tissue retention in two early Phase I studies in patients with colorectal cancer. (
  • 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. (
  • 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. (
  • 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. (
  • 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. (
  • They bind viral ligands such as hemagglutinins and hemagglutinin neuraminidases, some bacterial ligands and cellular ligands related with tumour growth such as PCNA . (
  • 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. (
  • 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 ). (
  • Tumor biomarkers act as important contextual cues or signals of cancer status. (
  • Although antigen-anti-Clec9A mAb conjugates target cross-presenting DCs, adjuvant must be codelivered for cytotoxic T lymphocyte (CTL) induction. (
  • 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. (
  • Cancer vaccines can be divided into six main categories: antigen/adjuvant vaccines, DNA vaccines, vector-based vaccines, tumor cell vaccines, dendritic cell vaccines and anti-idiotype vaccines. (
  • 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. (
  • 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. (
  • Potentially tumour-causing in primates and humans, it is used in laboratory research and in vaccines. (
  • Now that we have identified several tumor antigens and the immune response they provoke, we have made progress in developing cancer vaccines. (
  • Tumor cell-based vaccines are another vital area of research. (
  • Tumor-specific criteria are generally more useful than infection-based criteria. (
  • 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 ). (
  • The vaccination site increasingly resembles a viral infection, with lots of damaged normal tissue and antigens," Overwijk says. (
  • 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. (
  • 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. (
  • 4) Anti-viral drugs including acyclovir, vidarabine, famciclovir, valacyclovir, pencyclovir are widely used in the treatment of HSV-1 infection. (
  • [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. (
  • Antiviral effect of NO in various viral infections has also been documented. (
  • Considerable evidence suggests that an effective CD8 T-cell response can control or eradicate viral infections. (
  • 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). (
  • Characterization of T Antigens, Including Middle T and Alternative T, Expressed by the Human Polyomavirus Associated with Trichodysplasia Spinulosa. (
  • 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. (
  • Asymmetric assembly of Merkel cell polyomavirus large T-antigen origin binding domains at the viral origin. (
  • Specific carcinoembryonic antigens of the human digestive system. (
  • The detection of carcinoembryonic antigen in whole serum from patients with malignant and nonmalignant disease. (
  • The DNA tumor virus simian virus 40 produces the Large T antigen which. (
  • Simian virus 40 (SV40) accomplishes this task by producing the highly oncogenic large T antigen. (
  • This antigen is from the simian vacuolating virus 40 (SV40). (
  • 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. (
  • This enhances the anti-tumor immune response to tumor antigens released following viral lysis and provides a patient-specific vaccine. (
  • For many years researchers have presumed that tumor antigens useful for a vaccine strategy exist, but these have stubbornly eluded scientific capture. (
  • 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. (
  • 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. (
  • The p53 tumor suppressor binds to the Helicase domain and requires residue 350 through 627. (
  • 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. (
  • Fbw7 is itself an important tumor suppressor which makes it an attractive choice for inactivation by Large T," explained Dr. Markus Welcker, the study's first author. (
  • In the Journal of Biological Chemistry paper, Dr. Welcker and Dr. Bruce Clurman report that T antigen also binds to another tumor suppressor, Fbw7. (
  • I think this work underlines the importance of Fbw7 as an emerging tumor suppressor and the consequences of its loss in tumors," Dr. Welcker emphasized. (
  • 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. (
  • 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. (
  • 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. (
  • 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. (
  • Modular Three-component Delivery System Facilitates HLA Class I Antigen Presentation and CD8(+) T-cell Activation Against Tumors. (
  • Targeting a CAR to the TRAC locus with CRISPR/Cas9 enhances tumour rejection. (
  • This latter observation suggests that there are T cell-intrinsic mechanisms that contribute to failed de novo immune-mediated tumor rejection. (
  • 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. (
  • 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. (
  • Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. (
  • 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. (
  • 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. (
  • 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. (
  • 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. (
  • We can take a dendritic cell and import tumor antigens into it by a variety of mechanisms. (
  • Researchers at Thomas Jefferson University in Philadelphia, PA, supported in part by NuView Life Sciences, have published an article in the Journal of Nuclear Medicine reporting preclinical results of a novel PET biomarker designed to selectively detect malignant breast tumors. (
  • Organ and tumour antigens in malignant disease: a review. (
  • Crucial to this effort has been the belief that tumors display antigens -- distinct molecular landmarks on their cell surfaces -- that betray the malignant nature of the cell within and might therefore incite an immune response. (
  • 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. (
  • 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. (
  • In oncogenic polyomaviruses, the tumor antigens are responsible for the transformation activity, although the exact molecular mechanisms vary from one virus to another. (
  • Fundamental cell and molecular biological questions are addressed, with investigative approaches including viral oncogenesis, growth factors and oncogenes in developmental models, programmed cell death and drug resistance. (
  • 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 ). (
  • There appear to be distinct tumor site differences in the combined exposure risks, suggesting that different molecular pathways are involved. (
  • 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 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. (
  • 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. (
  • The study also evaluated site-specific HNC survival and recurrence by HPV E6/E7 antibody status compared to HPV tumor tissue status associated with tobacco and alcohol. (
  • For more than a century doctors have nourished the hope of enlisting the immune system in the battle against cancer -- specifically, of manipulating the immune system so that it will track down and eliminate tumors and the spreading seeds of malignancy, known as metastases, in much the way it tracks down and eliminates viruses and other pathogens. (
  • 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. (
  • The need for viral vectors has slowed down research and clinical use as their manufacturing and testing is lengthy and expensive. (
  • We identified 9 minor histocompatibility antigens (MiHA) as targets for alloreactivity, of which 8 were novel HLA class II restricted MiHA. (
  • Expression of the tumor antigen in a viral vector may facilitate appropriate antigen presentation. (

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