Precision Immunotherapy Alliance, The University of Oslo, Oslo, Norway.
Department of Cancer Immunology, Institute for Cancer Research Oslo, Oslo University Hospital, Oslo, Norway.
Nat Rev Immunol. 2024 Sep;24(9):680-693. doi: 10.1038/s41577-024-01022-8. Epub 2024 Apr 24.
Allogeneic cellular immunotherapies hold a great promise for cancer treatment owing to their potential cost-effectiveness, scalability and on-demand availability. However, immune rejection of adoptively transferred allogeneic T and natural killer (NK) cells is a substantial obstacle to achieving clinical responses that are comparable to responses obtained with current autologous chimeric antigen receptor T cell therapies. In this Perspective, we discuss strategies to confer cell-intrinsic, immune-evasive properties to allogeneic T cells and NK cells in order to prevent or delay their immune rejection, thereby widening the therapeutic window. We discuss how common viral and cancer immune escape mechanisms can serve as a blueprint for improving the persistence of off-the-shelf allogeneic cell therapies. The prospects of harnessing genome editing and synthetic biology to design cell-based precision immunotherapies extend beyond programming target specificities and require careful consideration of innate and adaptive responses in the recipient that may curtail the biodistribution, in vivo expansion and persistence of cellular therapeutics.
同种异体细胞免疫疗法具有很大的治疗癌症的潜力，因为它们具有潜在的成本效益、可扩展性和按需可用性。然而，过继转移的同种异体 T 细胞和自然杀伤 (NK) 细胞的免疫排斥是实现与目前的自体嵌合抗原受体 T 细胞疗法相当的临床反应的一个重大障碍。在本观点中，我们讨论了赋予同种异体 T 细胞和 NK 细胞内在免疫逃避特性的策略，以防止或延迟其免疫排斥，从而扩大治疗窗口。我们讨论了常见的病毒和癌症免疫逃逸机制如何作为改进现成的同种异体细胞疗法持久性的蓝图。利用基因组编辑和合成生物学来设计基于细胞的精确免疫疗法的前景超出了编程靶特异性的范畴，需要仔细考虑受者中的固有和适应性反应，这些反应可能会限制细胞治疗的生物分布、体内扩增和持久性。
