Department of Immunology, School of Basic Medical Sciences, NHC Key Laboratory of Medical Immunology (Peking University), Peking University Health Science Center, Beijing, 100191, China.
Sci China Life Sci. 2019 May;62(5):633-639. doi: 10.1007/s11427-018-9451-0. Epub 2019 Feb 15.
Introducing chimeric antigen receptor into immune cells against malignancies has contributed to a revolutionary innovation in cancer immunotherapy. As an important type of adaptive immune cells, T cells first caught researchers' attention and became great success in chimeric antigen receptor-based immunotherapy. However, engineered T cells seem to hit their bottleneck when resistance of cancerous cells, less encouraging responses in solid tumors and unwanted toxicities to the host remain to be solved. Meanwhile, innate immune cells get to join the race. Representatives such as natural killer cells, natural killer T cells, γδT cells and macrophages also prove to be well redirected with chimeric antigen receptors. Compared to chimeric antigen receptor engineered T cells, these engineered innate immune cells may possess multiple targeting and killing mechanisms, have the potential to crack the barrier of solid tumors and have less side effects in the host. Besides, possible universal access to cell resources and improvements in expansion and transduction techniques make these cells promising candidates with huge potential in translational medicine. Therefore, innate immune cells claim a brand-new dimension and are likely to supplement T cells greatly in the field of chimeric antigen receptor-based immunotherapy.
将嵌合抗原受体引入针对恶性肿瘤的免疫细胞中，促成了癌症免疫治疗的革命性创新。作为重要的适应性免疫细胞类型之一，T 细胞首先引起了研究人员的关注，并在嵌合抗原受体免疫疗法中取得了巨大成功。然而，当癌细胞产生耐药性、实体瘤中的反应不太理想以及对宿主产生不必要的毒性等问题仍待解决时，经过基因工程改造的 T 细胞似乎遇到了瓶颈。与此同时，先天免疫细胞也加入了这场竞赛。自然杀伤细胞、自然杀伤 T 细胞、γδT 细胞和巨噬细胞等代表细胞也被证明可以通过嵌合抗原受体有效地重定向。与基因工程改造的 T 细胞相比，这些经过基因工程改造的先天免疫细胞可能具有多种靶向和杀伤机制，有潜力破解实体瘤的屏障，并且在宿主中产生的副作用较小。此外，细胞资源的广泛应用以及扩增和转导技术的改进，使得这些细胞成为转化医学中极具潜力的候选者。因此，先天免疫细胞开辟了全新的维度，有可能在嵌合抗原受体免疫疗法领域极大地补充 T 细胞。
