肿瘤细胞治疗研究
英文原题：Chimeric antigen receptor T cells as adjuvant therapy for unresectable adenocarcinoma.
此外，我们开发了一种此前未被探索的体内毒性模型，用于在具有免疫能力的C57BL/6小鼠中评估安全性及对伤口愈合的影响。
实体瘤手术切除不完全是原发治疗失败的风险因素。在此，我们研究了CAR-T 细胞（CARTs）是否可作为辅助治疗以清除残留癌细胞。我们在两种部分切除异种移植模型中，使用间皮素特异性 CARTs 测试了该方法的可行性。此外，我们建立了一种此前未探索的体内毒性模型，以评估免疫健全 C57BL/6 小鼠中的安全性及对伤口愈合的影响。我们发现，在基于纤维蛋白胶的载体中局部递送 CARTs 可有效清除手术不完全后的残留癌细胞。与接受手术及无纤维蛋白胶 CARTs 治疗的小鼠相比，这显著延长了总生存期。靶向非肿瘤毒性减轻，且在任何小鼠中均未见伤口愈合并发症。基于这些观察，计划在局部晚期乳腺癌患者中开展临床试验。
Incomplete surgery of solid tumors is a risk factor for primary treatment failure. Here, we have investigated whether chimeric antigen receptor T cells (CARTs) could be used as an adjuvant therapy to clear residual cancer cells. We tested the feasibility of this approach in two partial resection xenograft models using mesothelin-specific CARTs. In addition, we developed a previously unexplored in vivo toxicity model to evaluate safety and effects on wound healing in immunocompetent C57BL/6 mice. We found that the local delivery of CARTs in a fibrin glue-based carrier was effective in clearing residual cancer cells following incomplete surgery. This resulted in significantly longer overall survival when compared to mice treated with surgery and CARTs without fibrin glue. On-target off-tumor toxicity was diminished, and wound healing complications were not seen in any of the mice. On the basis of these observations, a clinical trial in patients with locally advanced breast cancer is planned.
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