CELL INTELLIGENCE · 肿瘤细胞治疗研究

This phase 1 study evaluated the safety and feasibility of fully human anti-mesothelin chimeric antigen receptor-T cells (huCART-meso) in patients with lung adenocarcinoma, ovarian cancer, and mesothelioma. huCART-meso cells were administered intravenously, intrapleurally, and/or intraperitoneally with or without lymphodepletion. The huCART-meso cells are autologous T cells engineered to express a fully human extracellular single-chain antibody with mesothelin specificity and 4-1BB/TCR intracellular signaling domains. All patients (n = 20) received a dose of 1-3 10 7 CAR + cells/m 2 (1 patient with lung adenocarcinoma, 5 patients with mesothelioma, and 14 patients with ovarian cancer). Peak expansion was observed within the first 14 days, and huCART-meso cells were detectable in 16/20 patients at day 21 and in 5 patients at 12 months, with 1 patient showing detectable cells for over 2 years. The most common serious adverse event was cytokine release syndrome (7/20 patients, 35%). The best overall response was stable disease (12/20 patients, 60%), with a maximum reduction in target tumor volume of 41%. The median overall survival was 26.1 weeks, and the median progression-free survival was 12.3 weeks. These results establish the feasibility, safety, and preliminary efficacy of huCART-meso therapy, providing a rationale for future trials, ideally in combination with other therapies.