Parallel Comparison of 4-1BB or CD28 Co-stimulated CD19-Targeted CAR-T Cells for B Cell Non-Hodgkin’s Lymphoma

• Published in: Molecular therapy. Oncolytics Vol. 15; pp. 60 - 68
• Main Authors: Ying, Zhitao, He, Ting, Wang, Xiaopei, Zheng, Wen, Lin, Ningjing, Tu, Meifeng, Xie, Yan, Ping, Lingyan, Zhang, Chen, Liu, Weiping, Deng, Lijuan, Qi, Feifei, Ding, Yanping, Lu, Xin-an, Song, Yuqin, Zhu, Jun
• Format: Journal Article
• Language: English
• Published: Milwaukee Elsevier Inc 20.12.2019; Elsevier Limited; American Society of Gene & Cell Therapy; Elsevier
• Subjects: Antigens; B cell non-Hodgkin’s lymphoma; CD19 antigen; CD19-targeted chimeric antigen receptor-T cells; CD28 antigen; Chemotherapy; Chimeric antigen receptors; Clinical trials; co-stimulatory domain; Lymphocytes; Lymphocytes T; Lymphoma; Neurotoxicity; Non-Hodgkin's lymphoma; Patients; Studies; Tumor necrosis factor-TNF; B cell non-Hodgkin’s lymphoma; co-stimulatory domain; CD19-targeted chimeric antigen receptor-T cells
• ISSN: 2372-7705; 2372-7705
• DOI: 10.1016/j.omto.2019.08.002

CD19-targeted chimeric antigen receptor-T (CAR-T) cells with CD28 or 4-1BB (28z CAR-T and BBz CAR-T) have shown great promise to treat relapsed or refractory (r/r) B cell non-Hodgkin’s lymphoma (B-NHL). However, comparison of their clinical outcomes has never been reported. This study investigated their efficacy and adverse events in B-NHL therapy. Six patients with r/r B-NHL were initially enrolled and infused with 28z or BBz CAR-T cells at a dose of 0.75–5 × 105/kg. These CAR-T cells showed similar antitumor efficacies, with a complete response (CR) rate of 67% within 3 months. BBz CAR-T was well tolerated. However, severe cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome occurred in the 28z CAR-T cohort, resulting in the termination of further evaluation of 28z CAR-T. Three more patients were enrolled to investigate BBz CAR-T cells in-depth at an escalated dose (1 × 106/kg). All cases achieved CR within 3 months, and only grade 1/2 adverse events occurred. This study suggests that 4-1BB is more beneficial for the clinical performance of CAR-T cells than CD28 in CD19-targeted B-NHL therapy, at least under our manufacturing process. [Display omitted]