American Association for Cancer Research
10780432ccr193259-sup-230153_3_supp_6246434_q958z5.docx (1.66 MB)

Protocol of Study 1 from Chimeric Antigen Receptor-Glypican-3 T-Cell Therapy for Advanced Hepatocellular Carcinoma: Results of Phase I Trials

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journal contribution
posted on 2023-03-31, 21:48 authored by Donghua Shi, Yaoping Shi, Ahmed O. Kaseb, Xingxing Qi, Yuan Zhang, Jiachang Chi, Qing Lu, Huiping Gao, Hua Jiang, Huamao Wang, Daijing Yuan, Hong Ma, Hongyang Wang, Zonghai Li, Bo Zhai

CG1001- CAR-GPC3 T cells clinical trial


National Science and Technology

National Natural Science Foundation of China

Shanghai Science and Technology

Shanghai Jiao Tong University



Our preclinical studies demonstrated the potential of chimeric antigen receptor (CAR)-glypican-3 (GPC3) T-cell therapy for hepatocellular carcinoma (HCC). We report herein the first published results of CAR-GPC3 T-cell therapy for HCC. In two prospective phase I studies, adult patients with advanced GPC3+ HCC (Child-Pugh A) received autologous CAR-GPC3 T-cell therapy following cyclophosphamide- and fludarabine-induced lymphodepletion. The primary objective was to assess the treatment's safety. Adverse events were graded using the Common Terminology Criteria for Adverse Events (version 4.03). Tumor responses were evaluated using the RECIST (version 1.1). A total of 13 patients received a median of 19.9 × 108 CAR-GPC3 T cells by a data cutoff date of July 24, 2019. We observed pyrexia, decreased lymphocyte count, and cytokine release syndrome (CRS) in 13, 12, and nine patients, respectively. CRS (grade 1/2) was reversible in eight patients. One patient experienced grade 5 CRS. No patients had grade 3/4 neurotoxicity. The overall survival rates at 3 years, 1 year, and 6 months were 10.5%, 42.0%, and 50.3%, respectively, according to the Kaplan–Meier method. We confirmed two partial responses. One patient with sustained stable disease was alive after 44.2 months. CAR T-cell expansion tended to be positively associated with tumor response. This report demonstrated the initial safety profile of CAR-GPC3 T-cell therapy. We observed early signs of antitumor activity of CAR-GPC3 T cells in patients with advanced HCC.

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