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T-Cell Receptor-Like Antibodies: Targeting the Intracellular Proteome Therapeutic Potential and Clinical Applications

机译：T细胞受体样抗体：靶向细胞内蛋白质组治疗潜力和临床应用

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Major histocompatibility complex (MHC) class I molecules are key in the immune response against malignant cells by shaping the T-cell repertoire and presenting peptides from endogenous antigens to CD8+ cytotoxic T cells. Because of their unique specificity, MHC-peptide complexes are a desirable target for novel immunotherapeutic approaches. These complexes can be targeted by recombinant T-cell receptors (TCRs). However, most TCRs produced thus far have affinities which are too low for target detection under normal assay conditions, and limited stability (due to their generation in a single-chain version). Developing high-affinity soluble antibody molecules endowed with a TCR-like specificity toward tumor epitopes, termed TCR-like antibodies, addresses the low affinity of TCRs. These TCR-like antibodies are being developed as a new immunotherapeutic class for targeting tumor cells and mediating their specific killing. In addition, these antibodies are valuable research reagents enabling the study of human class I peptide-MHC ligand-presentation and TCR–peptide–MHC interactions.
机译：主要的组织相容性复合物（MHC）I类分子通过塑造T细胞库并将肽从内源性抗原呈递给CD8 +细胞毒性T细胞，是抵抗恶性细胞免疫反应的关键。由于其独特的特异性，MHC-肽复合物是新型免疫治疗方法的理想靶标。这些复合物可以被重组T细胞受体（TCR）靶向。但是，迄今为止生产的大多数TCR的亲和力对于正常检测条件下的靶标检测而言都太低，并且稳定性有限（由于它们以单链形式产生）。被赋予对肿瘤表位具有TCR样特异性的高亲和力可溶性抗体分子，称为TCR样抗体，解决了TCR的低亲和力。这些类TCR的抗体正在开发为一种新型的免疫疗法，用于靶向肿瘤细胞并介导其特异性杀伤作用。此外，这些抗体是有价值的研究试剂，可用于研究人类I类肽-MHC配体的表现形式和TCR-肽-MHC相互作用。

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