肿瘤细胞治疗研究
英文原题：Multimodal targeting of metastatic renal cell carcinoma via CD70-directed allogeneic CAR-NKT cells.
我们的发现共同支持 Allo CAR70-NKT 细胞作为一种下一代现货型免疫疗法的治疗潜力，其具有肿瘤与 TME 双重靶向功能，并额外具备清除同种反应性 T 细胞的能力，为治疗转移性肾细胞癌提供了极具吸引力的策略。
肾细胞癌（RCC）约占肾癌的90%；尽管已有现行治疗，仍有30%–40%的患者发生转移。靶向CD70的传统嵌合抗原受体（CAR）T细胞疗法显示出前景，但面临自体、个体化制备的挑战。在此，我们采用临床指导的培养方法，从造血干细胞和祖细胞制备靶向CD70的异基因CAR工程化不变型自然杀伤T（Allo CAR70-NKT）细胞。这些细胞可稳定扩增、纯度高，且不存在自相杀伤风险。Allo CAR70-NKT细胞通过CAR及自然杀伤（NK）受体介导的机制，对原发性和转移性RCC表现出强细胞毒性；并可通过T细胞受体（TCR）识别，选择性靶向免疫抑制性肿瘤微环境（TME）。此外，该细胞还能清除表达CD70的宿主异反应性T细胞，促进治疗持久性。综上，研究结果支持Allo CAR70-NKT细胞作为下一代现货型免疫疗法的治疗潜力；该疗法兼具靶向肿瘤和TME的双重功能，并可清除异反应性T细胞，为治疗转移性RCC提供了有吸引力的策略。
Renal cell carcinoma (RCC) represents about 90% of kidney cancers, with 30%-40% of patients developing metastatic disease despite current treatments. Conventional chimeric antigen receptor (CAR)-T therapy targeting CD70 shows promise but faces challenges due to its autologous, personalized nature. Here, we develop allogeneic CD70-directed CAR-engineered invariant natural killer T ( Allo CAR70-NKT) cells from hematopoietic stem and progenitor cells using a clinically guided culture method. These cells expand robustly with high purity and no fratricide risk. Allo CAR70-NKT cells exhibit potent cytotoxicity against primary and metastatic RCC via CAR- and natural killer (NK) receptor-mediated mechanisms and selectively target the immunosuppressive tumor microenvironment (TME) through T cell receptor (TCR) recognition. Additionally, they eliminate CD70 + host alloreactive T cells, promoting therapeutic persistence. Taken together, our findings support the therapeutic potential of Allo CAR70-NKT cells as a next-generation, off-the-shelf immunotherapy with dual tumor- and TME-targeting functionality and the added capacity to eliminate alloreactive T cells, which offers a compelling strategy for treating metastatic RCC.
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