Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China.
South Sichuan Institute of Translational Medicine, Luzhou, China.
Front Immunol. 2021 Mar 30;12:658753. doi: 10.3389/fimmu.2021.658753. eCollection 2021.
This review provides insight into the role of engineered T-cell receptors (TCRs) in immunotherapy. Novel approaches have been developed to boost anticancer immune system, including targeting new antigens, manufacturing new engineered or modified TCRs, and creating a safety switch for endo-suicide genes. In order to re-activate T cells against tumors, immune-mobilizing monoclonal TCRs against cancer (ImmTAC) have been developed as a novel class of manufactured molecules which are bispecific and recognize both cancer and T cells. The TCRs target special antigens such as NY-ESO-1, AHNAK or ERBB2 to boost the efficacy of anticancer immunotherapy. The safety of genetically modified T cells is very important. Therefore, this review discusses pros and cons of different approaches, such as ImmTAC, Herpes simplex virus thymidine kinase (HSV-TK), and inducible caspase-9 in cancer immunotherapy. Clinical trials related to TCR-T cell therapy and monoclonal antibodies designed for overcoming immunosuppression, and recent advances made in understanding how TCRs are additionally examined. New approaches that can better detect antigens and drive an effective T cell response are discussed as well.
这篇综述深入探讨了工程化 T 细胞受体（TCR）在免疫疗法中的作用。已经开发出了一些新的方法来增强抗癌免疫系统，包括靶向新抗原、制造新的工程化或修饰的 TCR 以及为内自杀基因创建安全开关。为了重新激活针对肿瘤的 T 细胞，已经开发了针对癌症的免疫动员单克隆 TCR（ImmTAC）作为一类新型的制造分子，它们是双特异性的，既能识别肿瘤又能识别 T 细胞。这些 TCR 针对 NY-ESO-1、AHNAK 或 ERBB2 等特殊抗原，以提高抗癌免疫疗法的疗效。基因修饰 T 细胞的安全性非常重要。因此，本文讨论了不同方法的优缺点，例如 ImmTAC、单纯疱疹病毒胸苷激酶（HSV-TK）和诱导型半胱天冬酶-9 在癌症免疫治疗中的应用。还讨论了与 TCR-T 细胞疗法相关的临床试验以及设计用于克服免疫抑制的单克隆抗体，以及最近在理解 TCR 如何进一步被检查方面取得的进展。还讨论了可以更好地检测抗原并驱动有效 T 细胞反应的新方法。
