Immune checkpoint inhibitors (ICIs) represent new therapeutic candidates against glioblastoma multiforme (GBM); however, their efficacy is clinically limited due to both local and systemic immunosuppressive environments. Hence, therapeutic approaches that stimulate local and systemic immune environments can improve the efficacy of ICIs. Here, we report an adoptive cell therapy employing neutrophils (NE) that are activated via surface attachment of drug‐free disk‐shaped backpacks, termed Cyto‐Adhesive Micro‐Patches (CAMPs) for treating GBM. CAMP‐adhered neutrophils (NE/CAMPs) significantly improved the efficacy of an anti‐PD1 antibody (aPD‐1) in a subcutaneous murine GBM model (GL261). A combination of NE/CAMPs and aPD‐1 completely regressed subcutaneous GL261 tumors in mice. The efficacy of NE/CAMPs against GBM was also tested in an orthotopic GL261 model. Neutrophil's ability to migrate into the brain was not affected by CAMP attachment, and intracerebral NE/CAMP accumulation was observed in mice‐bearing orthotopic GBM. The combination treatment of NE/CAMPs and aPD‐1 activated systemic immune responses mediated by T cells and showed improved therapeutic responses compared with aPD‐1 alone in the orthotopic GBM model. These results suggest that immunomodulation with NE/CAMPs offers a potential approach for the treatment of GBM by combination with ICIs.

中文翻译：

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使用背包激活的中性粒细胞对抗胶质母细胞瘤的免疫疗法


免疫检查点抑制剂（ICIs）代表了针对多形性胶质母细胞瘤（GBM）的新治疗候选者；然而，由于局部和全身免疫抑制环境，它们的疗效在临床上受到限制。因此，刺激局部和全身免疫环境的治疗方法可以提高 ICI 的疗效。在这里，我们报告了一种采用中性粒细胞（NE）的过继细胞疗法，通过无药盘形背包的表面附着激活中性粒细胞，称为细胞粘附微贴片（CAMP），用于治疗GBM。 CAMP 粘附的中性粒细胞 (NE/CAMP) 显着提高了皮下鼠 GBM 模型 (GL261) 中抗 PD1 抗体 (aPD-1) 的功效。 NE/CAMP 和 aPD-1 的组合使小鼠皮下 GL261 肿瘤完全消退。 NE/CAMP 对 GBM 的功效也在原位 GL261 模型中进行了测试。中性粒细胞迁移到大脑的能力不受 CAMP 附着的影响，并且在携带原位 GBM 的小鼠中观察到脑内 NE/CAMP 积聚。 NE/CAMP 和 aPD-1 的联合治疗激活了 T 细胞介导的全身免疫反应，并且在原位 GBM 模型中与单独使用 aPD-1 相比，显示出更好的治疗反应。这些结果表明，NE/CAMP 的免疫调节为联合 ICI 治疗 GBM 提供了一种潜在的方法。