肿瘤细胞治疗研究
英文原题：Targeting brain lesions of non-small cell lung cancer by enhancing CCL2-mediated CAR-T cell migration.
这些发现表明，通过CCR2b共表达来利用T细胞趋化性，是一种提高过继性T细胞疗法对伴有脑转移的实体瘤患者疗效的策略。
转移性非小细胞肺癌（NSCLC）在很大程度上仍无法治愈，一旦扩散到大脑，预后极差。特别是在脑转移患者中，血脑屏障（BBB）仍然是抗肿瘤药物和免疫细胞生物分布的显著障碍。在此，我们报道靶向B7-H3的嵌合抗原受体（CAR）T细胞（B7-H3.CAR）在体外对肿瘤细胞系和肺癌类器官表现出抗肿瘤活性，并在原位和转移性NSCLC异种移植模型中在体内表现出抗肿瘤活性。B7-H3.CAR-T细胞中共表达CCL2受体CCR2b，显著提高了其通过BBB的能力，增强了对脑肿瘤病灶的抗肿瘤活性。这些发现表明，通过CCR2b共表达来利用T细胞趋化性，代表了一种提高过继性T细胞疗法在伴有脑转移的实体瘤患者中疗效的策略。
Metastatic non-small cell lung cancer (NSCLC) remains largely incurable and the prognosis is extremely poor once it spreads to the brain. In particular, in patients with brain metastases, the blood brain barrier (BBB) remains a significant obstacle for the biodistribution of antitumor drugs and immune cells. Here we report that chimeric antigen receptor (CAR) T cells targeting B7-H3 (B7-H3.CAR) exhibit antitumor activity in vitro against tumor cell lines and lung cancer organoids, and in vivo in xenotransplant models of orthotopic and metastatic NSCLC. The co-expression of the CCL2 receptor CCR2b in B7-H3.CAR-T cells, significantly improves their capability of passing the BBB, providing enhanced antitumor activity against brain tumor lesions. These findings indicate that leveraging T-cell chemotaxis through CCR2b co-expression represents a strategy to improve the efficacy of adoptive T-cell therapies in patients with solid tumors presenting with brain metastases.
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