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  • epidermal growth f
  • Current studies demonstrated that various TAAs could act as target antigens for CAR-T cells, for instance, the type III variant epidermal growth factor receptor (EGFRvIII) was considered as an ideal target for its aberrant expression on the cell surface of several tumor types. (springermedizin.de)
  • In this review, we summarized the preclinical and clinical progress of CAR-T cells targeting EGFR, human epidermal growth factor receptor 2 (HER2), and mesothelin (MSLN), as well as the challenges for CAR-T cell therapy. (springermedizin.de)
  • cytokine
  • Initial studies of CAR T cell therapy have shown promising results in ovarian cancer, but there are some obstacles like impaired T cell trafficking, lack of antigenic targets, cytokine release syndrome and most important immunosuppressive tumor microenvironment. (springer.com)
  • Chen D, Heath V, O'Garra A, Johnston J, McMahon M (1999) Sustained activation of the raf-MEK-ERK pathway elicits cytokine unresponsiveness in T cells. (springer.com)
  • Supraphysiologic T-cell proliferation, a hallmark of this therapy, contributes to both efficacy and the most notable toxicity, cytokine release syndrome (CRS), posing a unique challenge for toxicity management. (bloodjournal.org)
  • Vα14 i NKT cells produce large amounts of cytokines rapidly after stimulation ( 4 ), and this cytokine burst may have a widespread influence on immune responses, including protection against autoimmune diseases, the host response to parasites and bacteria, and antitumor responses ( 2 , 3 , 5 - 8 ). (pnas.org)
  • Engagement of the TCR initiates positive (signal-enhancing) and negative (signal-attenuating) cascades that ultimately result in cellular proliferation, differentiation, cytokine production, and/or activation-induced cell death. (jimmunol.org)
  • Grade 3+ cytokine release syndrome was associated with polyfunctional T cells, and both grade 3+ neurologic toxicity (NT) and antitumor efficacy were associated with polyfunctional IL-17A-producing T cells. (bloodjournal.org)
  • Chmielewski M, Hombach AA, Abken H. Of CARs and TRUCKs: chimeric antigen receptor (CAR) T cells engineered with an inducible cytokine to modulate the tumor stroma. (springermedizin.de)
  • However, the adverse effects of CAR-T cell therapies are very severe like Cytokine Release syndrome (CRS) and on - target off - tumour toxicity. (sciencedomain.org)
  • ligand
  • Chang CC, Campoli M, Ferrone S. Classical and nonclassical HLA class I antigen and NK Cell-activating ligand changes in malignant cells: current challenges and future directions. (springer.com)
  • The interaction of the T cell receptor for antigen (TCR) with its antigen-major histocompatibility complex ligand is difficult to study because both are cell surface multimers. (sciencemag.org)
  • The CAR consists of an antibody or ligand-derived targeting ectodomain fused with a hinge, a trans-membrane domain, and intracellular T cell signaling domains. (frontiersin.org)
  • The prevailing view of thymocyte selection is that the fate of developing cells is dictated exclusively by the affinity/avidity of the expressed TCR for self-MHC/self-ligand. (jimmunol.org)
  • We found that CD5 is an inhibitory tuning receptor, and its surface expression is directly and proportionately regulated by the affinity of the TCR for selecting ligand. (jimmunol.org)
  • Interestingly, these signals are known to be either ligand-independent ('tonic' signals) or induced by ligand (antigen) binding to the BCR. (semanticscholar.org)
  • polypeptides
  • The four distinct T-cell antigen receptor polypeptides (alpha, beta, gamma, delta) form two different heterodimers (alpha:beta and gamma:delta) that are very similar to immunoglobulins in primary sequence, gene organization and modes of rearrangement. (nih.gov)
  • The receptors are non-covalently associated with a complex of several polypeptides collectively called cD3 antigens ( antigens, CD3 ). (biology-online.org)
  • avoids
  • This strategy thereby avoids the requirement of antigen processing and presentation by the target cell and is applicable to non-classical T cell targets like carbohydrates ( 3 ). (frontiersin.org)
  • lymphocyte
  • This is the basis for the graft-versus-leukemia (GVL) effect, which contributes in part to the efficacy of allogeneic stem cell transplantation (SCT) and is the rationale for donor lymphocyte infusion in leukemia. (bloodjournal.org)
  • The immunoglobulin G (IgG)-containing B lymphocyte antigen receptor (IgG-BCR) transmits a signal distinct from that of IgM-BCR or IgD-BCR, although all three use the same signal-transducing component, Igα/Igβ. (sciencemag.org)
  • It was observed that donor lymphocyte T cells could put patients who were relapsing into remission," said Dr. Schuster. (lymphomacoalition.org)
  • Expression
  • Also required for BCR surface expression and for efficient differentiation of pro- and pre-B-cells. (uniprot.org)
  • CAR expression on the surfaces of the T cells was detected by flow cytometry andWestern blot. (springer.com)
  • Analysis of T cell antigen receptor (TCR) expression by human peripheral blood CD4-8- alpha/beta T cells demonstrates preferential use of several V beta genes and an invariant TCR alpha chain. (rupress.org)
  • Analysis of TCR beta chains by quantitative PCR amplification demonstrated that the expression of four V beta gene families, V beta 2, 8, 11, and 13, was markedly increased in these DN alpha/beta T cell preparations. (rupress.org)
  • monoclonal
  • The addition of monoclonal antibodies to the antigen receptor complex on the malignant human T-cell line Jurkat generates increases in inositol trisphosphate and in the concentration of cytoplasmic free calcium. (pnas.org)
  • Immunity
  • Ideally, therapy for autoimmune diseases should eliminate pathogenic autoimmune cells while sparing protective immunity, but feasible strategies for such an approach have been elusive. (sciencemag.org)
  • Another approach in the development of immunotherapies is the use of cellular immunity with T cells. (lymphomacoalition.org)
  • pathway
  • Use of this pathway is plausible because of the enormous sequence diversity within the repertoire of V regions expressed by B cells. (jimmunol.org)
  • Prospects
  • This review will attempt to cover the basic concept and the applications of CAR-T cells, their adverse effects, challenges faced and the future prospects of the CAR-T cells in treatment of cancer. (sciencedomain.org)
  • immunoglobulin
  • The MCL BCR seems to be antigen-experienced since it shows biased immunoglobulin heavy variable (IGHV) gene usage and suggestive patterns of clonal diversification despite low levels of somatic hypermutation. (haematologica.org)
  • Porter DL
  • Maus MV, Grupp SA, Porter DL, June CH. Antibody-modified T cells: CARs take the front seat for hematologic malignancies. (springer.com)
  • activation
  • Bajpai UD, Zhang K, Teutsch M, Sen R, Wortis HH (2000) Bruton's tyrosine kinase links the B-cell receptor to nuclear factor kappaB activation. (springer.com)
  • Here, using α-GalCer-related compounds, we demonstrated that the full activation of Vα14 i NKT cells by glycolipids requires a stable and distinct type of TCR interaction. (pnas.org)
  • Overexpression of Gab2 in T cell lines inhibits TCR-evoked activation of the IL-2 promoter, blocking NF-AT- and NF-κB-directed transcription. (jimmunol.org)
  • Studies of Jurkat T cells treated with pharmacological inhibitors of PI3K (e.g., wortmannin, Ly294002) or transfected with dominant negative or activated mutants of PI3K suggest that PI3K inhibits TCR-evoked activation of the IL-2P ( 4 , 5 ). (jimmunol.org)
  • autoantibody
  • We engineered human T cells to express a chimeric autoantibody receptor (CAAR), consisting of the PV autoantigen, desmoglein (Dsg) 3, fused to CD137-CD3ζ signaling domains. (sciencemag.org)
  • After CD20-targeted depletion, serum autoantibody titers drop, indicating that short-lived plasmablasts are the source of autoantibodies in PV and targeting of CD20 + memory B cell precursors indirectly depletes autoantibody-secreting CD20 - plasmablasts ( 3 , 4 ). (sciencemag.org)
  • clinical
  • We have discussed basic functioning of CAR T cells, their rationale and clinical outcome in ovarian cancer with limitations. (springer.com)
  • While success has been achieved in a number of studies, and two CAR-T-cell products were recently approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) (YESCARTA ® , KYMRIAH ® ), this treatment modality continues to present challenges for clinical development. (springer.com)
  • The polyfunctionality strength index of manufactured CAR T cells were associated with clinical response and toxicities. (bloodjournal.org)
  • However, the association of preinfusion CAR product T-cell functionality with clinical outcomes has not been reported. (bloodjournal.org)
  • A prespecified T-cell polyfunctionality strength index (PSI) applied to preinfusion CAR product was significantly associated with clinical response, and PSI combined with CAR T cell-expansion or pretreatment serum IL-15 levels conferred additional significance. (bloodjournal.org)
  • Within the total product cell population, associations with clinical outcomes were greater with polyfunctional CD4+ T cells compared with CD8+ cells. (bloodjournal.org)
  • EGFRvIII
  • More importantly, EGFRvIII-CART specifically and efficiently recognized and killed A549-EGFRvIII cells with an effector/target ratio of 10:1 by expressing and releasing cytokines, including perforin, granzyme B, IFN-g, and TNF-α. (springer.com)
  • The in vivo study indicated that the metastasis of A549-EGFRvIII cells in mice were inhibited by EGFRvIII-CART cells, and the survival of the mice was significantly prolonged with no serious side effects. (springer.com)
  • EGFRvIII-CART showed significantly efficient antitumor activity against lung cancer cells expressing EGFRvIII in vivo and in vitro . (springer.com)
  • invariant
  • The self-reactivity of their T-cell antigen receptor (TCR) is thought to contribute to the development of immune regulatory cells, such as invariant NK T cells (iNKT). (pnas.org)
  • Invariant Vα14 rearrangement (Vα14 i ) natural killer (NK) T cells constitute the most numerous glycolipid-reactive population identified in mice, and a homologous population of Vα24 i NKT cells is present in humans ( 2 , 3 ). (pnas.org)
  • Vα14 i NKT cells bear a T cell antigen receptor (TCR) containing an invariant Vα14-Jα18 rearrangement paired preferentially with either Vβ8.2, Vβ7, or Vβ2 ( 9 ). (pnas.org)
  • rearrangement
  • Random cloning also identified a precise V alpha 7.2-J alpha (IGRJa14) rearrangement, with two variable amino acids encoded in the V-J junction, which was enriched in the DN alpha/beta T cell preparations from some, but not all, donors. (rupress.org)
  • novel
  • Our findings provide the first evidence of a negative function for a scaffolding adapter in T cells and identify Gab2/PI3K-containing complexes as novel regulators of TCR signaling. (jimmunol.org)
  • Bruton's
  • Defects in the gene encoding Bruton's tyrosine kinase (Btk) result in a disease called X-linked agammaglobulinemia, in which there is a profound decrease of mature B cells due to a block in B cell development. (rupress.org)