肿瘤细胞治疗研究
英文原题：IL-15 and IL-21 synergy improves anti-tumor efficacy of iPSC-derived cytotoxic T cells in solid tumors.
这些发现表明，可以将细胞因子协同作用工程化到iPSC衍生的T细胞中，以克服实体瘤免疫治疗中的重大障碍，为开发下一代现货型CAR-T疗法提供了一种可扩展的方法。
开发针对实体瘤的有效细胞免疫疗法需要具备强大的浸润、持久性、增殖和抗原特异性细胞毒性。在此，我们构建了转导嵌合抗原受体（iCAR-T细胞）的诱导多能干细胞（iPSC）来源的细胞毒性T细胞，并确定了一种最优的细胞因子装甲策略。IL-15和IL-21的共表达协同增强了STAT1磷酸化，导致趋化因子受体CXCR3的转录激活增加，从而改善了肿瘤归巢能力。此外，工程化iCAR-T细胞在肿瘤中维持了CD45RA - CD45RO + CCR7 + CD62L + 记忆T细胞样表型，有助于延长动物模型的生存期。这些发现表明，细胞因子协同作用可以被工程化到iPSC来源的T细胞中，以克服实体瘤免疫治疗中的重大障碍，为开发下一代现货型CAR-T疗法提供了一种可扩展的方法。
The development of effective cellular immunotherapies for solid tumors requires the presence of robust infiltration, persistence, proliferation, and antigen-specific cytotoxicity. Here, we engineered induced pluripotent stem cell (iPSC)-derived cytotoxic T cells transduced with a chimeric antigen receptor (iCAR-T cells) and identified an optimal cytokine armoring strategy. Co-expression of interleukin-15 (IL-15) and IL-21 synergistically enhanced STAT1 phosphorylation, leading to increased transcriptional activation of the chemokine receptor CXCR3 and thereby improving tumor homing capacity. Furthermore, the engineered iCAR-T cells maintained a CD45RA - CD45RO + CCR7 + CD62L + memory T cell-like phenotype in tumors, contributing to the prolonged survival of the animal model. These findings demonstrate that cytokine synergy can be engineered into iPSC-derived T cells to overcome significant barriers in solid tumor immunotherapy, offering a scalable approach to developing next-generation off-the-shelf CAR-T therapies.
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