Innovative Immunotherapies Unit, Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Scientific Institute, 20132, Milan, Italy.
Vita-Salute San Raffaele University, Milan, Italy.
Cancer Metastasis Rev. 2024 Dec;43(4):1279-1296. doi: 10.1007/s10555-024-10213-7. Epub 2024 Sep 24.
CAR T cell therapy, hailed as a breakthrough in cancer treatment due to its remarkable outcomes in hematological malignancies, encounters significant hurdles when applied to solid tumors. While notable responses to CAR T cells remain sporadic in these patients, challenges persist due to issues such as on-target off-tumor toxicity, difficulties in their trafficking and infiltration into the tumor, and the presence of a hostile and immunosuppressive microenvironment. This review aims to explore recent endeavors aimed at overcoming these obstacles in CAR T cell therapy for solid tumors. Specifically, we will delve into promising strategies for enhancing tumor specificity through antigen targeting, addressing tumor heterogeneity, overcoming physical barriers, and counteracting the immune-suppressive microenvironment.
嵌合抗原受体 T 细胞疗法(CAR T 细胞疗法)在血液恶性肿瘤的治疗中取得了显著的效果,被誉为癌症治疗的突破,但将其应用于实体瘤时却面临着重大障碍。尽管 CAR T 细胞在这些患者中仍会产生显著的反应,但由于脱靶毒性、在肿瘤中的运输和浸润困难以及存在敌对和免疫抑制的微环境等问题,挑战依然存在。本综述旨在探讨近期为克服 CAR T 细胞治疗实体瘤中这些障碍而进行的努力。具体而言,我们将深入探讨通过抗原靶向、解决肿瘤异质性、克服物理障碍和对抗免疫抑制微环境来提高肿瘤特异性的有前途的策略。