Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Suzhou Cancer Center Core Laboratory, Suzhou Municipal Hospital, Gusu School, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China.
Front Immunol. 2022 Jul 12;13:936496. doi: 10.3389/fimmu.2022.936496. eCollection 2022.
Chimeric antigen receptor (CAR)-T cells have enormous potentials for clinical therapies. The CAR-T therapy has been approved for treating hematological malignancies. However, their application is limited in solid tumors owing to antigen loss and mutation, physical barriers, and an immunosuppressive tumor microenvironment. To overcome the challenges of CAR-T, increasing efforts are put into developing CAR-T to expand its applied ranges. Varied receptors are utilized for recognizing tumor-associated antigens and relieving immunosuppression. Emerging co-stimulatory signaling is employed for CAR-T activation. Furthermore, other immune cells such as NK cells and macrophages have manifested potential for delivering CAR. Hence, we collected and summarized the last advancements of CAR engineering from three aspects, namely, the ectodomains, endogenous domains, and immune cells, aiming to inspire the design of next-generation adoptive immunotherapy for treating solid tumors.
嵌合抗原受体 (CAR)-T 细胞在临床治疗方面具有巨大的潜力。CAR-T 疗法已被批准用于治疗血液系统恶性肿瘤。然而，由于抗原丢失和突变、物理屏障以及免疫抑制性肿瘤微环境，其在实体瘤中的应用受到限制。为了克服 CAR-T 的挑战，人们正在努力开发 CAR-T，以扩大其应用范围。不同的受体被用于识别肿瘤相关抗原和解除免疫抑制。新兴的共刺激信号被用于 CAR-T 的激活。此外，NK 细胞和巨噬细胞等其他免疫细胞也表现出递送 CAR 的潜力。因此，我们从胞外结构域、内源性结构域和免疫细胞三个方面收集和总结了 CAR 工程的最新进展，旨在为设计用于治疗实体瘤的下一代过继免疫疗法提供灵感。
