a Roche Pharmaceutical Research & Early Development , Roche Innovation Center Zurich , Schlieren , Switzerland.
b Center of Integrated Protein Science Munich (CIPS-M) and Division of Clinical Pharmacology, Department of Medicine IV , Klinikum der Universität München, LMU, Member of the German Center for Lung Research (DZL) , Munich , Germany.
MAbs. 2019 May/Jun;11(4):621-631. doi: 10.1080/19420862.2019.1596511. Epub 2019 Apr 17.
Chimeric antigen receptor (CAR)-engineered T cells have a proven efficacy for the treatment of refractory hematological B cell malignancies. While often accompanied by side effects, CAR-T technology is getting more mature and will become an important treatment option for various tumor indications. In this review, we summarize emerging approaches that aim to further evolve CAR-T cell therapy based on combinations of so-called universal or modular CAR-(modCAR-)T cells, and their respective adaptor molecules (CAR-adaptors), which mediate the crosslinking between target and effector cells. The activity of such modCAR-T cells is entirely dependent on binding of the respective CAR-adaptor to both a tumor antigen and to the CAR-expressing T cell. Contrary to conventional CAR-T cells, where the immunological synapse is established by direct interaction of CAR and membrane-bound target, modCAR-T cells provide a highly flexible and customizable development of the CAR-T cell concept and offer an additional possibility to control T cell activity.
嵌合抗原受体 (CAR)-修饰的 T 细胞在治疗难治性血液学 B 细胞恶性肿瘤方面已被证实具有疗效。虽然经常伴随着副作用，但 CAR-T 技术越来越成熟，将成为各种肿瘤适应症的重要治疗选择。在这篇综述中，我们总结了新兴的方法，旨在通过所谓的通用或模块化 CAR-(modCAR-)T 细胞及其各自的衔接分子 (CAR-adaptors) 的组合，进一步发展 CAR-T 细胞疗法，这些衔接分子介导靶细胞和效应细胞之间的交联。这些 modCAR-T 细胞的活性完全取决于各自的 CAR-adaptor 与肿瘤抗原和表达 CAR 的 T 细胞的结合。与传统的 CAR-T 细胞不同，其中免疫突触是通过 CAR 与膜结合靶标的直接相互作用建立的，modCAR-T 细胞为 CAR-T 细胞概念的开发提供了高度灵活和可定制的可能性，并提供了控制 T 细胞活性的额外可能性。
