i3S, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal.
IPATIMUP, Institute of Molecular Pathology and Immunology, University of Porto, Portugal.
FEBS Lett. 2022 Feb;596(4):403-416. doi: 10.1002/1873-3468.14270. Epub 2022 Jan 12.
Chimeric antigen receptor (CAR)-T-cell therapy is a promising anticancer treatment that exploits the host's immune system to fight cancer. CAR-T cell therapy relies on immune cells being modified to express an artificial receptor targeting cancer-specific markers, and infused into the patients where they will recognize and eliminate the tumour. Although CAR-T cell therapy has produced encouraging outcomes in patients with haematologic malignancies, solid tumours remain challenging to treat, mainly due to the lack of cancer-specific molecular targets and the hostile, often immunosuppressive, tumour microenvironment. CAR-T cell therapy also depends on the quality of the injected product, which is closely connected to CAR design. Here, we explain the technology of CAR-Ts, focusing on the composition of CARs, their application, and limitations in cancer therapy, as well as on the current strategies to overcome the challenges encountered. We also address potential future targets to overcome the flaws of CAR-T cell technology in the treatment of cancer, emphasizing glycan antigens, the aberrant forms of which attain high tumour-specific expression, as promising targets for CAR-T cell therapy.
嵌合抗原受体 (CAR)-T 细胞疗法是一种有前途的抗癌治疗方法，利用宿主的免疫系统来对抗癌症。CAR-T 细胞疗法依赖于对免疫细胞进行修饰，使其表达靶向癌症特异性标志物的人工受体，并将其输注到患者体内，使其能够识别和消除肿瘤。尽管 CAR-T 细胞疗法在血液恶性肿瘤患者中产生了令人鼓舞的结果，但实体瘤仍然难以治疗，主要是因为缺乏癌症特异性分子靶点和恶劣的、常常是免疫抑制的肿瘤微环境。CAR-T 细胞疗法还取决于注入产品的质量，这与 CAR 设计密切相关。在这里，我们解释了 CAR-T 的技术，重点介绍了 CAR 的组成、它们在癌症治疗中的应用和局限性，以及克服所遇到的挑战的当前策略。我们还探讨了潜在的未来靶点，以克服 CAR-T 细胞技术在癌症治疗中的缺陷，强调糖抗原，其异常形式获得高肿瘤特异性表达，是 CAR-T 细胞疗法的有前途的靶点。
