Chimeric antigen receptor (CAR)-T cell therapy is a revolutionary new pillar in cancer treatment. Although treatment with CAR-T cells has produced remarkable clinical responses with certain subsets of B cell leukemia or lymphoma, many challenges limit the therapeutic efficacy of CAR-T cells in solid tumors and hematological malignancies. Barriers to effective CAR-T cell therapy include severe life-threatening toxicities, modest anti-tumor activity, antigen escape, restricted trafficking, and limited tumor infiltration. In addition, the host and tumor microenvironment interactions with CAR-T cells critically alter CAR-T cell function. Furthermore, a complex workforce is required to develop and implement these treatments. In order to overcome these significant challenges, innovative strategies and approaches to engineer more powerful CAR-T cells with improved anti-tumor activity and decreased toxicity are necessary. In this review, we discuss recent innovations in CAR-T cell engineering to improve clinical efficacy in both hematological malignancy and solid tumors and strategies to overcome limitations of CAR-T cell therapy in both hematological malignancy and solid tumors.
嵌合抗原受体（CAR）-T细胞疗法是癌症治疗领域一项革命性的新支柱。尽管CAR-T细胞治疗在特定B细胞白血病或淋巴瘤亚型中已产生显著的临床应答，但在实体瘤和血液系统恶性肿瘤治疗中仍面临诸多挑战。有效CAR-T细胞治疗的主要障碍包括：严重危及生命的毒性反应、抗肿瘤活性有限、抗原逃逸现象、靶向迁移受限以及肿瘤浸润不足。此外，宿主及肿瘤微环境与CAR-T细胞的相互作用会关键性地改变其功能。同时，开发和实施该疗法需要复杂的专业团队支持。为克服这些重大挑战，亟需通过创新策略与方法设计出抗肿瘤活性更强、毒性更低的增强型CAR-T细胞。本文综述了近年来通过CAR-T细胞工程技术创新提升血液系统恶性肿瘤和实体瘤临床疗效的研究进展，并探讨了克服两类肿瘤治疗局限性的应对策略。
CAR-T cell therapy: current limitations and potential strategies
肿瘤(癌症)患者之家