表达可诱导 IL-7 和 CCL19 的抗 CD19 CAR-T 细胞在复发/难治性大 B 细胞淋巴瘤患者中的安全性与可行性

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 10 6 -4.

0 10 6 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.