Department of Pharmacology, All India Institute of Medical Sciences, Bhubaneswar, Odisha, India.
Clinical Pharmacologist, Armed Forces Medical Services, Guwahati, India.
Eur J Haematol. 2024 Feb;112(2):211-222. doi: 10.1111/ejh.14101. Epub 2023 Sep 13.
Chimeric Antigen Receptor T-cell (CAR-T cell) therapy has emerged as a groundbreaking immunotherapeutic approach for treating various hematological malignancies. CAR-T cells are engineered to express synthetic receptors that target specific antigens on cancer cells, leading to their eradication. While the therapy has shown remarkable efficacy, a significant challenge that has been observed in 30%-70% of patients showing recurrent disease is antigen loss or downregulation. We searched PubMed/MEDLINE, EMBASE, and Google scholar for articles on antigen loss/escape following Chimeric antigen receptor T-cell therapy in malignancies. Antigen loss refers to the loss or reduction in the expression of the target antigen on cancer cells, rendering CAR-T cells ineffective. This phenomenon poses a significant clinical concern, as it can lead to disease relapse and limited treatment options. This review explores the mechanisms underlying antigen loss following CAR-T cell therapy, its implications on treatment outcomes, and potential strategies to overcome the problem.
嵌合抗原受体 T 细胞（CAR-T 细胞）疗法已成为治疗各种血液恶性肿瘤的突破性免疫治疗方法。CAR-T 细胞经过工程改造，表达靶向癌细胞特定抗原的合成受体，从而导致其被清除。虽然该疗法显示出显著的疗效，但在 30%-70%的复发疾病患者中观察到的一个重大挑战是抗原丢失或下调。我们在 PubMed/MEDLINE、EMBASE 和 Google Scholar 上搜索了关于嵌合抗原受体 T 细胞治疗恶性肿瘤后抗原丢失/逃逸的文章。抗原丢失是指癌细胞表面靶抗原的丢失或减少，使 CAR-T 细胞无效。这种现象引起了人们的极大关注，因为它可能导致疾病复发和有限的治疗选择。本综述探讨了 CAR-T 细胞治疗后抗原丢失的机制、对治疗结果的影响以及克服该问题的潜在策略。
