Laboratoire de Biochimie et Thérapies Moléculaires, Faculté de Pharmacie, Université Saint Joseph de Beyrouth, Beirut 1100, Lebanon.
Université de Paris, CNRS, INSERM, UTCBS, Unité des Technologies Chimiques et Biologiques pour la Santé, F-75006 Paris, France.
Int J Mol Sci. 2020 Nov 16;21(22):8620. doi: 10.3390/ijms21228620.
Immunoadoptive therapy with genetically modified T lymphocytes expressing chimeric antigen receptors (CARs) has revolutionized the treatment of patients with hematologic cancers. Although clinical outcomes in B-cell malignancies are impressive, researchers are seeking to enhance the activity, persistence, and also safety of CAR-T cell therapy-notably with a view to mitigating potentially serious or even life-threatening adverse events like on-target/off-tumor toxicity and (in particular) cytokine release syndrome. A variety of safety strategies have been developed by replacing or adding various components (such as OFF- and ON-switch CARs) or by combining multi-antigen-targeting OR-, AND- and NOT-gate CAR-T cells. This research has laid the foundations for a whole new generation of therapeutic CAR-T cells. Here, we review the most promising CAR-T cell safety strategies and the corresponding preclinical and clinical studies.
免疫过继疗法采用表达嵌合抗原受体 (CAR) 的基因修饰 T 淋巴细胞，彻底改变了血液系统恶性肿瘤患者的治疗方式。尽管 CAR-T 细胞疗法在 B 细胞恶性肿瘤中的临床疗效令人瞩目，但研究人员仍在寻求提高 CAR-T 细胞的活性、持久性和安全性，特别是旨在减轻潜在的严重甚至危及生命的不良事件，如靶向肿瘤外毒性和（特别是）细胞因子释放综合征。通过替换或添加各种组件（如 OFF-和 ON-switch CARs）或组合多抗原靶向 OR、AND 和 NOT 门控 CAR-T 细胞，已经开发出多种安全策略。这项研究为新一代治疗性 CAR-T 细胞奠定了基础。在这里，我们回顾了最有前途的 CAR-T 细胞安全策略及其相应的临床前和临床研究。
