Li Yan-Ruide, Zhu Yichen, Chen Yuning, Yang Lili
Department of Microbiology, Immunology, and Molecular Genetics (MIMG), University of California Los Angeles, Los Angeles, CA 90095, USA; Department of Bioengineering, University of California Los Angeles, Los Angeles, CA 90095, USA.
Department of Microbiology, Immunology, and Molecular Genetics (MIMG), University of California Los Angeles, Los Angeles, CA 90095, USA; Department of Bioengineering, University of California Los Angeles, Los Angeles, CA 90095, USA.
Trends Cancer. 2025 Jun;11(6):520-539. doi: 10.1016/j.trecan.2025.03.001. Epub 2025 Mar 27.
Unconventional T cells, such as invariant natural killer T (iNKT), γδ T, and mucosal-associated invariant T (MAIT) cells, play a pivotal role in bridging innate and adaptive immunity. Their capacity for rapid tumor targeting and effective modulation of the tumor microenvironment (TME) makes them promising candidates for cancer immunotherapy. Advances in chimeric antigen receptor (CAR) engineering have further highlighted their therapeutic potential, particularly for treating challenging cancers. Notably, these cells exhibit favorable safety profiles, enhancing their viability as off-the-shelf therapeutic options. We provide a comprehensive analysis of the clinical applications of CAR-engineered unconventional T cells, focusing on genetic modifications, manufacturing processes, preconditioning regimens, and dosing strategies. We discuss successful examples from recent clinical trials and explore future directions for utilizing these cells in cancer therapy and beyond.
非常规T细胞，如不变自然杀伤T（iNKT）细胞、γδT细胞和黏膜相关不变T（MAIT）细胞，在连接固有免疫和适应性免疫方面发挥着关键作用。它们快速靶向肿瘤并有效调节肿瘤微环境（TME）的能力使其成为癌症免疫治疗的有希望的候选者。嵌合抗原受体（CAR）工程的进展进一步凸显了它们的治疗潜力，特别是对于治疗具有挑战性的癌症。值得注意的是，这些细胞表现出良好的安全性，增强了它们作为现成治疗选择的可行性。我们对CAR工程化非常规T细胞的临床应用进行了全面分析，重点关注基因改造、制造工艺、预处理方案和给药策略。我们讨论了近期临床试验中的成功案例，并探索了在癌症治疗及其他领域利用这些细胞的未来方向。
