肿瘤细胞治疗研究
英文原题：Anti-PD-1 Nanobody-Armored MSLN CAR-T Therapy for Malignant Mesothelioma: Preclinical and Clinical Studies.
这些发现表明，NAC-T 细胞疗法对恶性间皮瘤患者而言是一种有前景的治疗策略。
恶性间皮瘤（MM）是一种侵袭性且目前无法治愈的癌症，治疗选择有限。鉴于间皮素在该肿瘤中高表达，研究者开发了经抗PD-1纳米抗体装甲化的间皮素靶向CAR-T细胞（NAC-T）。基于临床前体内外研究观察到的抗肿瘤活性增强，研究者启动了首个人体临床试验。11例标准治疗后疾病进展的恶性间皮瘤患者，在接受淋巴细胞清除后，静脉输注每千克5–20×10^6个NAC-T细胞。治疗耐受性良好，未观察到剂量限制性毒性。总缓解率为63.6%，其中1例完全缓解；疾病控制率为100%。无进展生存期中位数为5.0个月，总生存期中位数为25.6个月。对不同应答患者开展的T细胞受体和单细胞测序分析显示，特定T细胞亚型发生克隆扩增，且对肿瘤相关抗原的反应增强。这些发现提示，NAC-T细胞疗法是恶性间皮瘤患者一种有前景的治疗策略。
Malignant mesothelioma (MM) is an aggressive and currently incurable cancer with limited therapeutic options. Due to the high expression of mesothelin in this cancer, anti-PD-1 nanobody-armored mesothelin-targeting CAR-T (NAC-T) cells are developed. Based on the enhanced anti-tumor activity observed in preclinical in vitro and in vivo studies, a first-in-human clinical trial is initiated. Eleven patients with malignant mesothelioma who have progressed after standard therapies receive intravenous infusions of 5-20 10 6 per kg NAC-T cells following lymphodepletion. The treatment is well tolerated, with no dose-limiting toxicity observed. The overall response rate is 63.6%, including one complete response, and the disease control rate is 100%. The median progression-free survival is 5.0 months, and the median overall survival is 25.6 months. Moreover, T cell receptor and single-cell sequencing analyses in patients with varying responses revealed specific clonal expansion of T cell subtypes and enhanced reactivity to tumor-associated antigens. These findings suggest that NAC-T cell therapy represents a promising therapeutic strategy for patients with malignant mesothelioma.
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