Tumor Immunology Group, Laboratory of Experimental Hematology, Vaccine & Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, 2610 Antwerp, Belgium.
Center for Cell Therapy & Regenerative Medicine, Antwerp University Hospital, 2650 Edegem, Belgium.
Cells. 2020 Jul 18;9(7):1720. doi: 10.3390/cells9071720.
Over the past decades, adoptive transfer of T cells has revolutionized cancer immunotherapy. In particular, T-cell receptor (TCR) engineering of T cells has marked important milestones in developing more precise and personalized cancer immunotherapies. However, to get the most benefit out of this approach, understanding the role that TCR affinity, avidity, and functional avidity play on how TCRs and T cells function in the context of tumor-associated antigen (TAA) recognition is vital to keep generating improved adoptive T-cell therapies. Aside from TCR-related parameters, other critical factors that govern T-cell activation are the effect of TCR co-receptors on TCR-peptide-major histocompatibility complex (pMHC) stabilization and TCR signaling, tumor epitope density, and TCR expression levels in TCR-engineered T cells. In this review, we describe the key aspects governing TCR specificity, T-cell activation, and how these concepts can be applied to cancer-specific TCR redirection of T cells.
在过去的几十年中，T 细胞的过继转移彻底改变了癌症免疫疗法。特别是 T 细胞受体（TCR）工程技术在开发更精确和个性化的癌症免疫疗法方面取得了重要的里程碑。然而，为了从这种方法中获得最大的益处，了解 TCR 亲和力、亲合力和功能亲合力在 TCR 和 T 细胞在肿瘤相关抗原（TAA）识别背景下的功能中的作用对于不断产生改进的过继性 T 细胞疗法至关重要。除了 TCR 相关参数外，决定 T 细胞激活的其他关键因素是 TCR 共受体对 TCR-肽-主要组织相容性复合物（pMHC）稳定和 TCR 信号转导的影响、肿瘤表位密度以及 TCR 工程化 T 细胞中的 TCR 表达水平。在这篇综述中，我们描述了控制 TCR 特异性、T 细胞激活的关键方面，以及如何将这些概念应用于针对癌症特异性 TCR 的 T 细胞重定向。
