• In 2010, James Kochenderfer and colleagues achieved a breakthrough with a CAR T cell therapy, reporting tumour regression in a patient with advanced follicular lymphoma, who received two infusions of autologous T cells genetically engineered to express a CAR specifically recognizing the antigen CD19 expressed on B cells. (nature.com)
  • 3 Autologous lymphocytes genetically modified with the TCR for MART-1/Melan-A have been adoptively transferred to patients with advanced melanoma. (haematologica.org)
  • This phase II trial studies the side effects and how well white blood cells taken from person's own (autologous) cluster of differentiation (CD)8+ antigen-specific T cells, cyclophosphamide, aldesleukin, and ipilimumab work in treating patients with melanoma that has spread to another place in the body. (survivornet.com)
  • Autologous CD8+ antigen-specific T cells are white blood cells that are designed in the laboratory to find melanoma cells and may kill them. (survivornet.com)
  • Giving autologous CD8+ antigen-specific T cells with cyclophosphamide, aldesleukin, and ipilimumab may be an effective treatment for patients with metastatic melanoma. (survivornet.com)
  • Patients then receive autologous CD8+ melanoma-specific T cells IV over 30-60 minutes on day 0, aldesleukin subcutaneously (SC) twice daily (BID) on days 0-13 and ipilimumab IV over 90 minutes on days 1, 22, 43, and 64 in the absence of disease progression or unacceptable toxicity. (survivornet.com)
  • MART-1 27-35 -specific CTL could be effectively generated from a total of 11 of 12 PBL and from 3 of 3 TIL derived from HLA-A2 + melanoma patients, as well as from 2 of 4 PBL from HLA-A2 + healthy donors by in vitro stimulation with autologous PBMC pulsed with the synthetic MART-1 27-35 peptide. (elsevierpure.com)
  • By stimulating human lymphocytes with an autologous renal carcinoma, we obtained CTL recognizing an antigen derived from a novel, ubiquitous protein. (ox.ac.uk)
  • Protein melan-A also known as melanoma antigen recognized by T cells 1 or MART-1 is a protein that in humans is encoded by the MLANA or "MALENA" gene. (wikipedia.org)
  • at the National Cancer Institute coined the term MART-1, which stands for "melanoma antigen recognized by T-cells. (wikipedia.org)
  • Antibodies against the antigen are used in the medical specialty of anatomic pathology in order to recognize cells of melanocytic differentiation, useful for the diagnosis of a melanoma. (wikipedia.org)
  • This is due to the fact that its high precursor frequency of about 1/1000 among cytotoxic T-cells makes it easy for antigen presenting cells to evoke peptide-specific responses. (wikipedia.org)
  • In the oral mucosa, melanocytes are observed in a ratio of about 1 melanocyte to 10 basal cells. (medscape.com)
  • In 1989, Zelig Eshhar and colleagues realized that the inability of T cells to recognize surface tumour antigens could be overcome by replacing domains of the T cell receptor (TCR) with antibody parts with specificity towards proteins on these cells. (nature.com)
  • They combined the variable region of an antibody with the constant regions of the TCR chains, thus producing chimeric antigen receptors (CARs) that provided T cells with antibody-type specificity. (nature.com)
  • The T cells expressing CARs recognized and eliminated target cells, and produced interleukin 2 in the presence of the antigen, providing a proof of concept that this approach triggers a cellular immune response. (nature.com)
  • Physiologic recognition of tumour antigens by T cells is mediated by the TCR-CD3 complex. (nature.com)
  • In 2017, two studies - the phase II ZUMA-1 trial led by Sattva Neelapu and a case-series study led by Carl June - validated the efficacy of CD19 CAR T cells in patients with refractory B-cell leukaemia and lymphoma. (nature.com)
  • Another ACT developed in parallel to CAR T cells is engineering T cells to express TCRs that recognize tumour-associated antigens. (nature.com)
  • In 2006, Rosenberg and colleagues transferred TCR T cells specifically recognizing the melanoma antigen MART-1 in 15 patients, two of whom achieved regression and still showed high levels of engineered cells in circulation one year after the infusion. (nature.com)
  • Other successful studies quickly followed, such as those demonstrating sustained complete and partial responses in patients with melanoma and treatment of synovial cell sarcoma with TCR T cells against the NY-ESO-1 antigen. (nature.com)
  • The use of CD20 as suicide gene was investigated in CMV specific T cells and in T cells genetically modified with an antigen specific T-cell receptor. (haematologica.org)
  • 1 , 2 The anti-tumor effect of DLI is mediated by donor T cells recognizing allo-antigens on the malignant cells of the recipient. (haematologica.org)
  • Donor T cells may also induce GvHD due to recognition of allo-antigens on non-malignant tissues of the patient. (haematologica.org)
  • T-cell receptor (TCR) gene transfer is an attractive strategy for rapid in vitro generation of high numbers of antigen specific T cells. (haematologica.org)
  • 4 In addition, TCRs for minor histocompatibility antigens, including HA-1 and HA-2, have been transferred to donor-derived virus-specific T cells to treat patients with hematologic malignancies after allogeneic stem cell transplantation. (haematologica.org)
  • Although human CD20 has previously been described as functional selection marker and suicide gene after retroviral transfer to T lymphocytes, 9 , 10 the specificities of these T cells were unknown, and therefore a potential effect of CD20 on antigen-specific T-cell functions could not be investigated. (haematologica.org)
  • In the case of melanoma, circulating cells may find a suitable microenvironment in the first draining lymph node, known as the sentinel lymph node, in other lymphnodes or in distant organs, leading to secondary tumor growth (Figure 1 ). (hindawi.com)
  • Thus, the local immunological milieu in tissue compartments forms the nature and magnitude of the host responses, i.e., frequencies of regulatory T cells (Tregs) vs. T-helper 17 (Th17) cells, amount of pro-inflammatory cytokines vs. anti-inflammatory cytokines, extent of neutrophilia and antigen-presenting-cell (APC) activation, among others. (frontiersin.org)
  • Here, we investigate the in vivo functional activity and dynamics of the transferred cells by analyzing samples from 3 representative patients with melanoma enrolled in a clinical trial of ACT with TCR transgenic T cells targeted against the melanosomal antigen MART-1. (ca.gov)
  • The analyses included evaluating 19 secreted proteins from individual cells from phenotypically defined T-cell subpopulations, as well as the enumeration of T cells with TCR antigen specificity for 36 melanoma antigens. (ca.gov)
  • Antigen recognition by T cells bearing αβ T cell receptors (TCRs) is restricted by major histocompatibility complex (MHC). (rcsb.org)
  • However, how antigens are recognized by T cells bearing γδ TCRs remains unclear. (rcsb.org)
  • Although γδ T cells can recognize nonclassical MHC, it is generally thought that recognition of antigens is not MHC restricted. (rcsb.org)
  • Here, we took advantage of an in vitro system to generate antigen-specific human T cells and show that melanoma-associated antigens, MART-1 and gp100, can be recognized by γδ T cells in an MHC-restricted fashion. (rcsb.org)
  • Our work shows that antigen-specific and MHC-restricted γδ T cells can be generated in vitro and that MART-1-specific γδ T cells can also be found and cloned from the naïve repertoire. (rcsb.org)
  • DCs transfected with tumor-associated antigens are capable of stimulating antigen-specific T cells, but cytolytic responses have been disappointing. (duke.edu)
  • Studies have shown the HMB45-reactive antigen is present in cutaneous melanocytes, prenatal and infantile retinal pigment epithelium and melanoma cells. (dbs-india.com)
  • The MART-1/Melan A recognizes a protein of 18kDa, identified as MART-1 (Melanoma Antigen Recognized by T cells 1) or Melan-A (1). (dbs-india.com)
  • Evaluate the influence of anti-CTLA4 on the induction of T cells to non-targeted tumor-associated antigens (antigen-spreading) following adoptive transfer antigen-specific CTL, and the correlation of these responses with clinical outcome. (survivornet.com)
  • Gene modified dendritic cells (DC) are able to modulate DC functions and induce therapeutic immunity or tolerance in an antigen-specific manner. (biomedcentral.com)
  • We found that efficient gene transfer into pDC can be achieved with VSVG-pseudotyped lentiviral vectors (LV) under the control of phoshoglycerate kinase (PGK) and elongation factor-1 (EF1α) promoters (28% to 90% of E-GFP + cells, respectively) in the absence of phenotypic and functional maturation. (biomedcentral.com)
  • Benign smooth muscle tumors, or leiomyomas, are common, well-circumscribed neoplasms that can arise from smooth muscle cells anywhere in the body, but are encountered most commonly in the uterus [1]. (peertechzpublications.org)
  • Source of smooth muscle in the oral cavity may be the arterial tunica media, lingual duct, circumvallate papillae and pluripotential mesenchymal cells [1]. (peertechzpublications.org)
  • A peptide-based cancer vaccine consisting of amino acid residues 26 through 35 of MART-1 (melanoma antigen recognized by T-cells-1) with a leucine substitution at amino acid position 27 to improve immunogenicity. (medicalterminologydb.com)
  • Upon administration, MART-1:26-35(27L) peptide vaccine may induce a cytotoxic T-lymphocyte (CTL) response against MART-1-expressing tumor cells, resulting in decreased tumor growth. (medicalterminologydb.com)
  • The tumor-associated antigen (TAA) MART-1 may be overexpressed on melanoma cancer cells. (medicalterminologydb.com)
  • Activation induced cell death (AICD) of human melanoma antigen-specific TCR engineered CD8 T cells involves JNK, Bim and p53. (uchc.edu)
  • Knockdown of T-bet expression in Mart-127-35 -specific T-cell-receptor-engineered human CD4(+) CD25(-) and CD8(+) T cells attenuates effector function. (uchc.edu)
  • Death receptor-independent activation-induced cell death in human melanoma antigen-specific MHC class I-restricted TCR-engineered CD4 T cells. (uchc.edu)
  • Inhibition of superoxide generation upon T-cell receptor engagement rescues Mart-1(27-35)-reactive T cells from activation-induced cell death. (uchc.edu)
  • Silencing of endogenous IL-10 in human dendritic cells leads to the generation of an improved CTL response against human melanoma associated antigenic epitope, MART-1 27-35. (uchc.edu)
  • Antigen presentation by MART-1 adenovirus-transduced interleukin-10-polarized human monocyte-derived dendritic cells. (uchc.edu)
  • Anti-MART-1 35-43 -specific CTL could also be induced, but these T cells did not recognize melanoma cells. (elsevierpure.com)
  • These CTL lines specifically lysed and release cytokines (TNF-α, IFN-γ, and GM-CSF) in response to T2 cells pulsed with MART-1 27-35 , as well as to HLA-A2 + MART-1 + melanoma cells. (elsevierpure.com)
  • CTL generated with MART-1 27-35 also lysed uncultured HLA-A2 + melanoma cells derived from tumor biopsies, indicating that this MART-1 epitope is likely to be expressed in association with HLA-A2 on the surface of tumor cells in vivo. (elsevierpure.com)
  • HMB-45 and Ki-67 (MIB-1) labeled only rare neoplastic cells within the proliferative nodule. (elsevierpure.com)
  • Processing of some antigens by the standard proteasome but not by the immunoproteasome results in poor presentation by dendritic cells. (ox.ac.uk)
  • We show that dendritic cells also carry immunoproteasomes and fail to present this antigen. (ox.ac.uk)
  • For immunization with such antigens, proteins should be less suitable than peptides, which do not require proteasome digestion in dendritic cells. (ox.ac.uk)
  • Low recurrence rates for in situ and invasive melanomas using Mohs micrographic surgery with melanoma antigen recognized by T cells 1 (MART-1) immunostaining: tissue processing methodology to optimize pathologic staging and margin assessment. (jamanetwork.com)
  • AIM OF THE STUDY: In this study, we investigated the metabolic reprogramming and anti-metastasis/epithelial-mesenchymal transition (EMT) effects of AS exposure in Twist-overexpressing head and neck squamous cell carcinoma (HNSCC, OECM-1 and FaDu-Twist) cells. (bvsalud.org)
  • AS exposure inhibited Twist and hypoxia-inducible factor-1α (HIF-1α) protein and/or mRNA expression in Twist-overexpressing OECM-1 and FaDu-Twist cells. (bvsalud.org)
  • Furthermore, glucose uptake and lactate accumulation, together with HIF-1α-regulated glycolysis genes were diminished by AS in OECM-1 cells. (bvsalud.org)
  • AS decreased the ECAR, and enhanced the OCR together with basal respiration, ATP production, maximal respiration, and spare respiratory capacity under normoxia and hypoxia (CoCl2) in OECM-1 cells. (bvsalud.org)
  • while TCA cycle metabolites were increased by AS treatment in OECM-1 cells. (bvsalud.org)
  • CONCLUSIONS: We concluded that AS treatment suppresses EMT/metastasis and Warburg effects through Twist and HIF-1α inhibition in Twist-overexpressing HNSCC cells. (bvsalud.org)
  • MelanA was discovered as an antigen recognized by tumor infiltrating cytotoxic T cells from a melanoma patient, hence the name Melanoma Antigen (J Exp Med 1994;180:35). (enquirebio.com)
  • Vaccination with tumor lysate-pulsed dendritic cells elicits antigen-specific, cytotoxic T-cells in patients with malignant glioma. (nwbio.com)
  • Immature dendritic cells phagocytose apoptotic cells via alphavbeta5 and CD36, and cross-present antigens to cytotoxic T lymphocytes. (nwbio.com)
  • Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLs. (nwbio.com)
  • Babatz J, Röllig C, Löbel B, Folprecht G, Haack M, Günther H, Köhne CH, Ehninger G, Schmitz M, Bornhäuser M. Induction of cellular immune responses against carcinoembryonic antigen in patients with metastatic tumors after vaccination with altered peptide ligand-loaded dendritic cells. (nwbio.com)
  • After intracellular digesting, DCs present peptides produced from tumor-associated antigens in complicated with MHC course I substances to naive Compact disc8+ T-cells. (aboutsciencenow.info)
  • After that, the Compact disc8+ T-cell response is normally particular for tumor antigens and needs cross-presentation from the tumor antigens by professional APCs, such as for example dendritic cells. (aboutsciencenow.info)
  • Tumor derived, tumor associated antigens (TAA) or homing peptides are used as targets for the development of cancer vaccines (such as NY-ESO-1 peptide vaccine) as they illicit an immune response against cells containing the cancer antigen. (eurogentec.com)
  • Cellular antigens that are specific for MELANOMA cells. (bvsalud.org)
  • Cloning and transferring of MART-1-specific γδ TCRs restored the specific recognition of the initial antigen MHC/peptide reactivity and conferred antigen-specific functional responses. (rcsb.org)
  • MART-1 (26-35) has been shown to be better recognized by a number of polyclonal and monoclonal populations of tumor-reactive HLA-A*0201-restricted cytotoxic T lymphocytes (CTL) than MART-1 (27-35) (human). (cymitquimica.com)
  • Owing to differential expression in various tissues, some of these peptides serve as biomarkers and can also play immuno-modulatory roles within the immune landscape of cancer pathways such as Mucin, Melan-A-MART, PD-L1 etc. (eurogentec.com)
  • A crystal structure of a MART-1-specific γδ TCR, together with MHC/peptide, revealed distinctive but similar docking properties to those previously reported for αβ TCRs, recognizing MART-1 on HLA-A*0201. (rcsb.org)
  • This partnership validates our approach of using synthesized human T cell repertoires to generate safe and effective libraries to discover antigen specific TCRs at scale," said Elizabeth Wood, Ph.D., Founder & CEO, JURA Bio. (businesswire.com)
  • TCR and TIGIT chimeras retroviral constructs The and chains from your previously characterized TCRs specific for MART-126-35 termed F4 (or DMF4) and F5 (or DMF5) were subcloned into the MSGV1 vector as explained previously [30]. (biotechpatents.org)
  • Lack of cleavage by the immunoproteasome was also observed for melanoma differentiation antigen Melan-A26-35/HLA-A2, currently used for antitumoral vaccination. (ox.ac.uk)
  • of Belgium called the gene melan-A, presumably an abbreviation for "melanocyte antigen. (wikipedia.org)
  • The MART-1/melan-A antigen is specific for the melanocyte lineage, found in normal skin, the retina, and melanocytes, but not in other normal tissues. (wikipedia.org)
  • Macrophages as stimulators of MART-1 27-35 epitope-specific human cytolytic T lymphocytes in vitro. (uchc.edu)
  • MART-1 is an Ag expressed on melanomas and melanocytes, and is recognized by the majority of HLA-A2-restricted tumor-specific tumor-infiltrating lymphocytes (TIL) from melanoma patients. (elsevierpure.com)
  • Healthy humans develop spontaneous CD8+ T cell responses to melanoma associated antigens (MA) expressed by normal melanocytes. (mdpi.com)
  • MART-1/melan-A is a protein antigen that is found on the surface of melanocytes. (wikipedia.org)
  • MART-1/melan-A is a putative 13 kDa transmembrane protein consisting of 118 amino acids. (wikipedia.org)
  • Most of the studies on malignancy immunotherapy using DCs have been carried out for melanoma antigen presentation [9, 20, 34, 35]. (aboutsciencenow.info)
  • CONCLUSIONS: CD40L augments DC IL-12 secretion and is essential to potentiate specific antimelanoma cytolytic responses stimulated by the Mart-1 antigen. (duke.edu)
  • The combination of HMB45, MART-1 cocktail and Tyrosinase make this quadruple antibody cocktail a first-order pan melanoma screener, and may prove to be a valuable marker for melanoma metastasis in sentinel lymph nodes (1,2). (dbs-india.com)
  • Patients are mostly young and late diagnosis, which means thicker tumors (thicker than 1 mm, or Breslow index ≥1 mm: the Breslow index is the measurement in mm of the vertical thickness of the primary tumor) and/or involvement of regional lymph nodes, causes a greater risk of developing a disseminated disease. (hindawi.com)
  • These results demonstrate that MART-1 27-35 peptide may represent an ideal candidate for Ag-specific immunotherapy in melanoma patients. (elsevierpure.com)
  • Studies have shown Tyrosinase to be a more sensitive marker when compared to HMB45 and MART-1. (dbs-india.com)
  • 1 Department of Cutaneous Oncology and Comprehensive Melanoma Research Center, Moffitt Cancer Center, Tampa, Florida. (aacrjournals.org)
  • METHODS: Human monocyte-derived DCs were cultured and transfected with mRNA encoding full-length melanoma-associated antigen, Mart-1, and matured with and without sCD40L. (duke.edu)
  • I. Evaluate the influence of anti-CTLA4 on the duration of in vivo persistence and anti-tumor efficacy achieved following adoptive transfer of antigen-specific CTL. (survivornet.com)
  • Highly cancer-specific antigens derived from somatic mutations, the so-called neoantigens, occurring in individual cancers have been in focus recently. (cancerbiomed.org)
  • More recently, tumor specific antigens or tumor specific neoantigens (TSNA) that arise from tumor cell mutations are being identified in a large number of cancer patients. (eurogentec.com)
  • The names MART-1 and melan-A were coined by two groups of researchers who independently sequenced the gene for this antigen in 1994. (wikipedia.org)
  • The same name is also used to refer to the gene which codes for the antigen. (wikipedia.org)
  • The iPS cell-derived DCs possess the features of primary DCs like the capacity for T-cell stimulation, digesting and delivering antigens, and the ability of making cytokines. (aboutsciencenow.info)
  • Studies have also shown that MART-1 is more sensitive than HMB45 when labeling metastatic melanomas. (dbs-india.com)
  • TIGIT-28 improving capacity was also showed in an primary in vitro style of T-cell of hypofunction induction upon recurring antigen publicity. (biotechpatents.org)
  • Etomoxir supplier Open in a separate window Fig. 1 Design and manifestation of TIGIT-based CSRs, TCR F4 and CD155 ligand.a Schematic representation of the different TIGIT chimeras (while indicated). (biotechpatents.org)