Phase I clinical safety and efficacy observation of αPD-1-mesoCAR-T cells in the treatment of advanced gynecologic cancer

Autor: Yong Xia, Zhuqing Liu, Zhongzheng Zhu, Zhicai Lin, Hui Xue, Zongchang Song, Yanyan Yu, Xinhong Guan, Yuying Sun, Zhifeng Miao, Yaping Yang, Sitong Wang, Zhong Li, Linjie Lv, Qing Xu, Yan Sun, Jin-xing Lou, Qijun Qian
Rok vydání: 2022
Předmět:
Zdroj: Journal of Clinical Oncology. 40:e17535-e17535
ISSN: 1527-7755
0732-183X
DOI: 10.1200/jco.2022.40.16_suppl.e17535
Popis: e17535 Background: Ovarian cancer is the most lethal gynecologic malignancy and the fifth leading cause of cancer-related death among women. Most of patients often have refractory or relapse. We have developed a CAR T cell secreting PD-1 nanoantibodies and targeting mesothelin (αPD-1-mesoCAR-T) and conducted a phase I clinical trial for evaluation of safety and efficacy of the αPD-1-mesoCAR-T cells in gynecologic tumors. Methods: This study is a single-arm, open, dose-increasing clinical study and two infusions (interval 14-35 days). Patients with advanced gynecological cancer were enrolled when immunohistochemical analysis for positive mesothelin over 70% and failed second-line treatment in Mengchao Cancer Hospital affiliated to Shanghai University and Shanghai Tenth People's Hospital affiliated to Tongji University. All patients underwent lymphodepletion before infusion at a dose of 1 to 15x106/kg. CAR copies, nanobody levels, cytokines, T lymphocyte subtypes were determined before and after infusion. Results: a total of 7 patients were enrolled so far and completed the first evaluation. After treatment, most symptoms of the patients were alleviated, two patients (#2, #3) had their lesions decreased. By RECIST 1.1, all 7 patients’ diseases became stable, and the disease control rate was 100%. The PFS of #3 patient with stable disease (SD) was 5.3 months, the patient #2 was 4.1 months. The frequent adverse events were fever, fatigue, nausea and pruritus. No sever adverse events above grade 3 occurred. The number of CAR-T cells in the peripheral blood increased significantly during day 4-14 after the infusion, and the PD-1 nanoantibody levels and the contents of INF-γ、IL-6、IL-2 and MCP-1 also increased at day 1-4. Conclusions: The preliminary clinical study showed that the aPD-1-mesoCAR-T cells are safe for the treatment of gynecologic cancer and stabilized the diseases. More data of the treatment is warrantied to continually follow up these patients.
Databáze: OpenAIRE
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