肿瘤细胞治疗研究
英文原题：Validation of CCL20-driven CAR-γδ T secreting PD-1 blockade with enhanced trafficking into solid tumor.
CAR-T 细胞治疗实体瘤的主要挑战在于 CAR-T 细胞向肿瘤部位的高效递送与浸润，以及克服免疫抑制性肿瘤微环境。
CAR-T细胞治疗实体瘤的主要挑战包括如何有效递送并促进细胞浸润肿瘤部位，以及如何克服免疫抑制性肿瘤微环境。将趋化因子引导的迁移和递送与清除免疫抑制屏障相结合，是一种有前景的策略。研究者在非小细胞肺癌（NSCLC）细胞系来源异种移植（CDX）模型中，验证了一种靶向EGFR的CAR-T细胞CAR-E276；该细胞共同表达CCR6并分泌PD-1阻断分子。研究结果显示，将趋化因子、检查点阻断及T细胞功能特性整合进CAR-T细胞，可促进其有效迁移至肿瘤组织、延长持续存在，并产生强效肿瘤杀伤作用，且不诱发移植物抗宿主病（GvHD）。值得注意的是，CAR-E276还显示出用于现货型异体治疗的潜力。这些发现有望提供有价值的见解，并推动靶向实体瘤CAR-T疗法的开发。
The primary challenges of CAR-T cells for solid tumor treatment involve the efficient delivery and infiltration of CAR-T cells into the tumor site, as well as overcoming the immunosuppressive tumor microenvironment. Combining chemokine-guided trafficking and delivery with the clearance of immunosuppressive barriers represents a promising strategy. An EGFR-targeted CAR- T, CAR-E276 that co-expresses CCR6 and secretes PD1 blockade was in vivo validated using a non-small cell lung cancer (NSCLC) CDX model. The results from CAR-E276 indicated that integrating chemokines, checkpoint blockades, and T cell properties into CAR-T cells facilitated their efficient trafficking into tumor tissues, ensured prolonged persistence, and achieved robust tumor-killing effects without inducing GvHD. Notably, CAR-E276 also exhibited potential for off-the-shelf and allogeneic applications. These findings are expected to offer valuable insights and drive the development of CAR-T therapies targeting solid tumors.
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