Xun Xiaodong, Hao Jialing, Cheng Qian, Gao Pengji
Department of General Surgery, Beijing Jishuitan Hospital, Capital Medical University, Beijing 100035, China.
Beijing Research Institute of Traumatology and Orthopedics, Beijing 100035, China.
Biomedicines. 2025 Aug 19;13(8):2012. doi: 10.3390/biomedicines13082012.
Cellular immunotherapy has emerged as a transformative approach in oncology, revolutionizing cancer treatment paradigms. Since the groundbreaking development of induced pluripotent stem cells (iPSCs) by Yamanaka in 2008, significant progress has been made in generating various iPSCs-derived immunocytes, including T cells, dendritic cells, macrophages, natural killer (NK) cells, and B cells. These engineered immune cells offer unprecedented opportunities for personalized cancer therapy as they can be derived from patients' own cells to minimize immune rejection. In addition, various new techniques are being used for the induction and amplification of iPSCs-derived immunocytes, such as small-molecule techniques, 3D culture systems, nanotechnology, and animal models for the in vivo amplification of immunocytes. Of course, challenges remain in improving immunocyte characteristics. Targeting efficiency needs enhancement to better distinguish tumor cells from healthy tissue, while biological activity must be optimized for sustained antitumor effects. Safety concerns, particularly regarding potential off-target effects and cytokine release syndrome, require further investigation. The immunosuppressive nature of tumor microenvironment also poses significant hurdles for solid tumor treatment. Ongoing clinical trials are exploring the therapeutic potential of iPSCs-derived immunocytes, with researchers investigating combination therapies and genetic modifications to overcome current limitations.
细胞免疫疗法已成为肿瘤学领域一种变革性的方法，彻底改变了癌症治疗模式。自2008年山中伸弥开创性地开发诱导多能干细胞（iPSC）以来，在生成各种iPSC来源的免疫细胞方面取得了重大进展，包括T细胞、树突状细胞、巨噬细胞、自然杀伤（NK）细胞和B细胞。这些工程化免疫细胞为个性化癌症治疗提供了前所未有的机会，因为它们可以从患者自身细胞中获得，以尽量减少免疫排斥。此外，各种新技术正被用于诱导和扩增iPSC来源的免疫细胞，如小分子技术、3D培养系统、纳米技术以及用于免疫细胞体内扩增的动物模型。当然，在改善免疫细胞特性方面仍存在挑战。靶向效率需要提高，以便更好地区分肿瘤细胞和健康组织，同时必须优化生物活性以实现持续的抗肿瘤效果。安全问题，特别是潜在的脱靶效应和细胞因子释放综合征，需要进一步研究。肿瘤微环境的免疫抑制特性也给实体瘤治疗带来了重大障碍。正在进行的临床试验正在探索iPSC来源的免疫细胞的治疗潜力，研究人员正在研究联合疗法和基因修饰以克服当前的局限性。
