肿瘤细胞治疗研究
英文原题：Exploring the therapeutic efficacy difference in claudin18.2-targeted cell therapy revealed by single-cell sequencing.
CAR-T 细胞（CAR T）疗法已成功用于治疗血液系统恶性肿瘤。
CAR-T 细胞（CAR T）疗法已成功用于治疗血液系统恶性肿瘤。然而，其在实体瘤中的应用仍面临挑战。我们此前对正在进行的临床试验（NCT03874897）的分析显示，接受CT041 CAR T治疗的晚期CLDN18.2阳性胃癌患者取得了令人鼓舞的结果。在此，我们收集了该临床试验中5例患者在CT041输注后3天和7天的外周血和腹水。na ve样T细胞比例高的患者更可能从CT041治疗中获益。我们发现，腹水上皮细胞中CLDN18高表达与良好预后相关，而腹水上皮细胞中MYC高表达以及肿瘤细胞与T细胞之间强相互作用则是CT041治疗的不良预后因素。这些发现可能为筛选可从CAR T治疗中获益的人群以及提高CAR T治疗疗效提供理论依据。
Chimeric antigen receptor T cell (CAR T) therapy has been successfully used to treat hematological malignancies. Nonetheless, its application to solid tumors remains challenging. Our previous analysis of the ongoing clinical trial (NCT03874897) demonstrated promising results in patients with advanced CLDN18.2-positive gastric cancer who received CT041 CAR T treatment. Here, we collected peripheral blood and ascites from five patients from the clinical trial 3 and 7 days (d) after CT041 infusion. Patients with a high proportion of na ve-like T cells were more likely to benefit from CT041 treatment. We found that high expression of CLDN18 in ascites epithelial cells correlated with a favorable prognosis, whereas ascites epithelial cells with high MYC expression and strong interactions between tumor cells and T cells were adverse prognostic factors for CT041 treatment. These findings may provide theoretical evidence for the screening of populations that can benefit from CAR T therapy and improve the efficacy of CAR T therapy.
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