Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Immunol Rev. 2023 Nov;320(1):217-235. doi: 10.1111/imr.13255. Epub 2023 Aug 7.
Adoptive cellular therapy using chimeric antigen receptor (CAR) T cells has led to a paradigm shift in the treatment of various hematologic malignancies. However, the broad application of this approach for myeloid malignancies and solid cancers has been limited by the paucity and heterogeneity of target antigen expression, and lack of bona fide tumor-specific antigens that can be targeted without cross-reactivity against normal tissues. This may lead to unwanted on-target off-tumor toxicities that could undermine the desired antitumor effect. Recent advances in synthetic biology and genetic engineering have enabled reprogramming of immune effector cells to enhance their selectivity toward tumors, thus mitigating on-target off-tumor adverse effects. In this review, we outline the current strategies being explored to improve CAR selectivity toward tumor cells with a focus on natural killer (NK) cells, and the progress made in translating these strategies to the clinic.
嵌合抗原受体 (CAR) T 细胞过继细胞疗法在治疗各种血液系统恶性肿瘤方面带来了治疗模式的转变。然而，由于靶抗原表达的稀少性和异质性，以及缺乏可以靶向而不与正常组织发生交叉反应的真正肿瘤特异性抗原，这种方法在髓系恶性肿瘤和实体瘤中的广泛应用受到了限制。这可能导致不必要的靶内脱靶毒性，从而破坏理想的抗肿瘤效果。合成生物学和基因工程的最新进展使得免疫效应细胞的重编程成为可能，从而增强其对肿瘤的选择性，从而减轻靶内脱靶的不良反应。在这篇综述中，我们概述了目前正在探索的提高 CAR 对肿瘤细胞选择性的策略，重点是自然杀伤 (NK) 细胞，并介绍了将这些策略转化为临床应用的进展。
