研究动态
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对抗实体肿瘤的嵌合抗原受体免疫细胞:结构、机制、近期进展和未来发展。

Chimeric antigen receptor-immune cells against solid tumors: Structures, mechanisms, recent advances, and future developments.

发表日期:2023 Aug 28
作者: Xudong Li, Wei Li, Linping Xu, Yongping Song
来源: CHINESE MEDICAL JOURNAL

摘要:

嵌合抗原受体(CAR)T细胞免疫疗法的出现在治疗血液恶性肿瘤方面取得了突破。然而,它们在治疗实体肿瘤方面的成功受限。CAR -天然杀伤细胞(NK细胞)相比CAR-T细胞具有几个优势,因为NK细胞可以由现有的细胞系或单倍型不匹配的同种异体NK细胞制备而成,这意味着它们更有可能成为“现成货”。此外,它们可以通过CAR依赖/独立途径杀伤癌细胞,并且毒性有限。巨噬细胞是体内最具塑性的免疫细胞,它们能够有效地浸润到肿瘤内,并且在肿瘤微环境中(TMEs)中数量众多。重要的是,在几种实体瘤中,CAR-巨噬细胞(CAR-Ms)最近取得了令人兴奋的临床前结果。然而,CAR-T细胞、CAR-NK细胞和CAR-M都有各自的优势和局限性。在本综述中,我们系统地讨论CAR-T细胞、CAR-NK细胞和CAR-M的当前状态、进展和主要障碍,这些方面包括CAR结构、治疗机制、最新研究进展、当前挑战和解决方案以及根据现有研究的比较,旨在为将来治疗实体肿瘤提供合理选择。版权所有© 2023年中国医学协会,由沃特斯·克鲁尔公司根据CC-BY-NC-ND许可在其下制作。
The advent of chimeric antigen receptor (CAR)-T cell immunotherapies has led to breakthroughs in the treatment of hematological malignancies. However, their success in treating solid tumors has been limited. CAR-natural killer (NK) cells have several advantages over CAR-T cells because NK cells can be made from pre-existing cell lines or allogeneic NK cells with a mismatched major histocompatibility complex (MHC), which means they are more likely to become an "off-the-shelf" product. Moreover, they can kill cancer cells via CAR-dependent/independent pathways and have limited toxicity. Macrophages are the most malleable immune cells in the body. These cells can efficiently infiltrate into tumors and are present in large numbers in tumor microenvironments (TMEs). Importantly, CAR-macrophages (CAR-Ms) have recently yielded exciting preclinical results in several solid tumors. Nevertheless, CAR-T, CAR-NK, and CAR-M all have their own advantages and limitations. In this review, we systematically discuss the current status, progress, and the major hurdles of CAR-T cells, CAR-NK cells, and CAR-M as they relate to five aspects: CAR structure, therapeutic mechanisms, the latest research progress, current challenges and solutions, and comparison according to the existing research in order to provide a reasonable option for treating solid tumors in the future.Copyright © 2023 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.