肿瘤细胞治疗研究
英文原题：Utilizing induced neural stem cell-based delivery of a cytokine cocktail to enhance chimeric antigen receptor-modified T-cell therapy for brain cancer.
这些研究共同表明，联合细胞治疗平台具有提高 CAR-T 细胞疗法治疗脑肿瘤疗效的潜力。
嵌合抗原受体（CAR）修饰T细胞疗法在血液系统肿瘤治疗中显示出巨大临床潜力，但治疗实体瘤仍面临挑战。本研究考察一种新型联合细胞疗法的潜力：利用可归巢至肿瘤的诱导神经干细胞（iNSC）增强CAR-T细胞疗法，从而有效抑制脑肿瘤。体内外迁移实验显示，iNSC分泌的RANTES/IL-15使CAR-T细胞迁移增加6倍、扩增增加3倍，并在胶质母细胞瘤（GBM）模型中增强抗肿瘤活性。此外，多模态成像显示，iNSC递送RANTES/IL-15并联合静脉给予CAR-T细胞，可在第一周内使已形成的原位GBM异种移植瘤缩小25至38倍，随后肿瘤缓解持续至治疗后60天。相比之下，单用CAR-T仅能部分控制肿瘤生长，中位生存期仅19天。总之，这些研究显示联合细胞治疗平台有望提高CAR-T治疗脑肿瘤的疗效。
Chimeric antigen receptor (CAR)-modified T-cell therapy has shown enormous clinical promise against blood cancers, yet efficacy against solid tumors remains a challenge. Here, we investigated the potential of a new combination cell therapy, where tumor-homing induced neural stem cells (iNSCs) are used to enhance CAR-T-cell therapy and achieve efficacious suppression of brain tumors. Using in vitro and in vivo migration assays, we found iNSC-secreted RANTES/IL-15 increased CAR-T-cell migration sixfold and expansion threefold, resulting in greater antitumor activity in a glioblastoma (GBM) tumor model. Furthermore, multimodal imaging showed iNSC delivery of RANTES/IL-15 in combination with intravenous administration of CAR-T cells reduced established orthotopic GBM xenografts 2538-fold within the first week, followed by durable tumor remission through 60 days post-treatment. By contrast, CAR-T-cell therapy alone only partially controlled tumor growth, with a median survival of only 19 days. Together, these studies demonstrate the potential of combined cell therapy platforms to improve the efficacy of CAR-T-cell therapy for brain tumors.
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