Multicenter phase 1 trial of 4-1BB co-stimulated CD19-specific CAR-NK cell therapy for refractory/relapsed large B cell lymphoma

CAR-modified NK (CAR-NK) cells are candidates for next-generation cancer immunotherapies. In a multicenter dose-escalation phase 1 trial in China, 8 patients with relapsed/refractory large B cell lymphoma received repeititve administration of CAR-NK cells with 4-1BB and CD3ζ signalling endo-domains. No dose-limiting toxicities occurred, and the maximum tolerated dose was not reached. No cases of cytokine release syndrome, neurotoxicity, or graft-versus-host disease were observed. The overall response rate was 62.5% at day 30, with 4 patients (50%) achieving complete response. The median progression-free survival was 9.5 months, and the median overall survival was not reached. The study met the pre-specified endpoints, The authors conclude that CD19-BBz CAR-NK cells were feasible and therapeutically safe, and capable of inducing durable response in patients with B cell lymphoma.