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用嵌合受体靶向实体瘤抗原:癌症生物学与合成免疫学相遇。

Targeting solid tumor antigens with chimeric receptors: cancer biology meets synthetic immunology.

机构信息

Cellular Immunotherapy Program, Cancer Center, Massachusetts General Hospital, Boston, USA; Harvard Medical School, Boston, MA, USA; Department of Pathology, Massachusetts General Hospital, Boston, MA, USA.

Cellular Immunotherapy Program, Cancer Center, Massachusetts General Hospital, Boston, USA; Harvard Medical School, Boston, MA, USA; Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA.

出版信息

Trends Cancer. 2024 Apr;10(4):312-331. doi: 10.1016/j.trecan.2024.01.003. Epub 2024 Feb 13.

Abstract

Chimeric antigen receptor (CAR) T cell therapy is a medical breakthrough in the treatment of B cell malignancies. There is intensive focus on developing solid tumor-targeted CAR-T cell therapies. Although clinically approved CAR-T cell therapies target B cell lineage antigens, solid tumor targets include neoantigens and tumor-associated antigens (TAAs) with diverse roles in tumor biology. Multiple early-stage clinical trials now report encouraging signs of efficacy for CAR-T cell therapies that target solid tumors. We review the landscape of solid tumor target antigens from the perspective of cancer biology and gene regulation, together with emerging clinical data for CAR-T cells targeting these antigens. We then discuss emerging synthetic biology strategies and their application in the clinical development of novel cellular immunotherapies.

摘要

嵌合抗原受体 (CAR) T 细胞疗法是治疗 B 细胞恶性肿瘤的医学突破。目前正在集中精力开发针对实体瘤的 CAR-T 细胞疗法。尽管临床上已批准的 CAR-T 细胞疗法针对 B 细胞谱系抗原,但实体瘤的靶点包括新抗原和肿瘤相关抗原 (TAA),它们在肿瘤生物学中具有多种作用。目前多项早期临床试验报告了针对实体瘤的 CAR-T 细胞疗法的令人鼓舞的疗效迹象。我们从癌症生物学和基因调控的角度回顾了实体瘤靶抗原的情况,并结合了针对这些抗原的 CAR-T 细胞的新兴临床数据。然后,我们讨论了新兴的合成生物学策略及其在新型细胞免疫疗法的临床开发中的应用。

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