肿瘤细胞治疗研究
英文原题：Pluripotent stem cell-derived CAR-NK progenitor therapy targets minimal residual disease and prevents relapse in leukemia models.
降低化疗后的复发率仍是提高肿瘤治疗疗效的一大挑战。
降低化疗后复发率仍是改善癌症治疗的一项重大挑战。在此，我们在白血病模型中开发了一种多能干细胞来源的诱导自然杀伤（NK）谱系定向祖细胞（iNKP）细胞疗法。我们通过类器官培养系统产生了大量 iNKP 细胞。经工程化改造以表达 C-X-C 基序趋化因子受体 4（CXCR4）和嵌合抗原受体（CARs）的 iNKP 细胞，可高效迁移至骨髓并产生 CAR-iNK 细胞，这些细胞在多个器官和外周血中持续存在超过 80 天。值得注意的是，CAR-iNKP 细胞输注精准保护动物免受肿瘤攻击。此外，在常规化疗后单次低剂量输注 CAR-iNKP 细胞减少了微小残留病，并显著预防了人 CD19 + B-ALL 和 CD7 + T-ALL 荷瘤动物的癌症复发。CAR-iNKP 细胞治疗解决了传统 CAR-NK 细胞输注的局限性，并为未来在人类癌症治疗中的应用提供了新策略。
Reducing relapse rates post-chemotherapy remains a major challenge for improving cancer therapy. Here, we developed a pluripotent stem cell-derived induced natural killer (NK) lineage-committed progenitor (iNKP) cell therapy in leukemia models. We generated abundant iNKP cells via an organoid culture system. The iNKP cells, engineered to express C-X-C motif chemokine receptor 4 (CXCR4) and chimeric antigen receptors (CARs), efficiently migrated to the bone marrow and generated CAR-iNK cells, which persisted in multiple organs and peripheral blood for over 80 days. Notably, CAR-iNKP cell infusion precisely protected animals from tumor challenges. Furthermore, a single low-dose infusion of CAR-iNKP cells following conventional chemotherapy reduced minimal residual disease and significantly prevented cancer relapse in human CD19 + B-ALL and CD7 + T-ALL tumor-bearing animals. CAR-iNKP cell treatment addresses the limitations of traditional CAR-NK cell infusion and offers a new strategy for future application in human cancer therapy.
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