Annexin V apoptosis detection kit ; 62700 ;
Cell Discov. 2024 Jan 9;10(1):5. doi: 10.1038/s41421-023-00625-0.
Wen Lei # 1 2, Ai Zhao # 3 4, Hui Liu # 1 2, Chunmei Yang 2, Cheng Wei 3, Shanshan Guo 1, Zhilu Chen 5, Qunyi Guo 6, Linjie Li 7, Mingzhe Zhao 8, Gongqiang Wu 9, Guifang Ouyang 10, Ming Liu 11, Jinyi Zhang 12, Jimin Gao 13 14, Wenbin Qian 15 16
Affiliations expand
- PMID: 38191529
- PMCID: PMC10774422
- DOI: 10.1038/s41421-023-00625-0
Abstract
Although CD19-specific chimeric antigen receptor (CAR) T cells are curative for patients with relapsed or refractory large B-cell lymphoma (R/R LBCL), disease relapse with tumor antigen-positive remains a challenge. Cytokine/chemokine-expressing CAR-T cells could overcome a suppressive milieu, but the clinical safety and efficacy of this CAR-T therapy remain unclear. Here we report the preclinical development of CD19-specific CAR-T cells capable of expressing interleukin (IL)-7 and chemokine (C-C motif) ligand (CCL)-19 upon CD19 engagement (referred to as 7 × 19 CAR-T cells) and results from a phase 1 and expansion phase trial of 7 × 19 CAR-T cell therapy in patients with R/R LBCL (NCT03258047). In dose-escalation phase, there were no dose-limiting toxicities observed. 39 patients with R/R LBCL received 7 × 19 CAR-T with doses ranged from 0.5 × 106-4.0 × 106 cells per kg body weight. Grade 3 cytokine release syndrome occurred in 5 (12.8%) patients and ≥ grade 3 neurotoxicity in 4 (10.3%) patients. The overall response rate at 3 months post-single infusion was 79.5% (complete remission, 56.4%; partial response, 23.1%). With a median follow-up of 32 months, the median progression-free survival was 13 months, and median overall survival was not reached, with an estimated rate of 53.8% (95% CI, 40.3% to 72.0%) at two years. Together, these long-term follow-up data from the multicenter clinical study suggest that 7 × 19 CAR-T cells can induce durable responses with a median overall survival of greater than 2 years, and have a manageable safety profile in patients with R/R LBCL.