Molecular Therapy Oncolytics

https://doi.org/10.1016/j.omto.2019.08.002

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

Zhitao Ying, Ting He, Xiaopei Wang, Wen Zheng, Ningjing Lin, Meifeng Tu, Yan Xie, Lingyan Ping, Chen Zhang, Weiping Liu, Lijuan Deng, Feifei Qi, Yanping Ding, Xin-An Lu, Yuqin Song, Jun Zhu

Abstract

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.

Keywords: B cell non-Hodgkin’s lymphoma; CD19-targeted chimeric antigen receptor-T cells; co-stimulatory domain.