School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia.
School of Biomedical Engineering, Sun Yat-sen University, Guangzhou, Guangdong, China.
Front Immunol. 2022 Oct 31;13:984864. doi: 10.3389/fimmu.2022.984864. eCollection 2022.
Chimeric antigen receptor T cell (CAR-T) therapy is novel tumor immunotherapy that enables autologous T to express synthetic receptors to specifically recognize the surface tumor-associated antigens for exerting subsequent antitumor effects, and eliminating the resistance, metastases and recurrence of cancer. Although CAR T cells have exhibited success in eradicating hematologic malignancies, their applications to solid tumors has not yet been achieved due to obstacles such as the immune-suppressor tumor microenvironment and lack of tumor specific target antigens. In this review, we presented advancements in the development of CAR T cell therapy in solid tumors, and offered a brief summary of the challenges, as well as novel engineering and pharmaceutical interventions to overcome these barriers. Looking forward, we discussed the latest studies which are expected to reach the clinicals in the next few years, including CRISPR screens-based CAR modification and CAR T cells driven from progenitor-like T cells. Collectively, this review may inspire researchers and clinicians to develop clinical available strategies of CAR T cell therapies in solid tumor.
嵌合抗原受体 T 细胞（CAR-T）疗法是一种新型的肿瘤免疫疗法，它使自体 T 细胞能够表达合成受体，从而特异性识别表面肿瘤相关抗原，发挥后续的抗肿瘤作用，并消除癌症的耐药性、转移和复发。尽管 CAR-T 细胞在消除血液恶性肿瘤方面取得了成功，但由于免疫抑制性肿瘤微环境和缺乏肿瘤特异性靶抗原等障碍，其在实体瘤中的应用尚未实现。在这篇综述中，我们介绍了 CAR-T 细胞疗法在实体瘤中的发展进展，并简要总结了克服这些障碍的挑战以及新的工程和药物干预措施。展望未来，我们讨论了预计在未来几年内进入临床阶段的最新研究，包括基于 CRISPR 筛选的 CAR 修饰和由祖细胞样 T 细胞驱动的 CAR-T 细胞。总之，这篇综述可能会激发研究人员和临床医生开发实体瘤中 CAR-T 细胞治疗的临床可用策略。
