Rapid Production and Clinical Efficacy of Anti-CD19/CD22 Dual CAR T-Cell Therapy in B-ALL

A novel manufacturing process for anti-CD19/CD22 dual CAR-T therapy, named GC022F, has been developed and evaluated in a phase I clinical trial (NCT04129099) for its application in treating B-cell acute lymphoblastic leukemia (B-ALL). This approach utilizes a FasTCAR™ platform that significantly reduces production time to 24 hours, contrasting with the traditional 9-14 days required for conventional dual CAR-T cells. The phase I study aimed to assess the safety and effectiveness of GC022F, with patients receiving a conditioning treatment followed by the infusion of the therapy.

GC022F cells demonstrated several advantages over the conventional GC022C cells, including reduced exhaustion, a younger phenotype, greater in vitro expansion, and enhanced anti-leukemia efficacy in a mouse model. In vivo studies revealed that GC022F was more potent, reducing tumor burden more rapidly and leading to prolonged survival in the animals.

Between November 2019 and June 2020, ten patients with B-ALL were enrolled in the study, receiving varying doses of GC022F. The median observation time was 99 days, with patients ranging in age from 3 to 48 years. Notably, GC022F showed a favorable safety profile, with no grade 3 or higher cytokine release syndrome (CRS) or neurotoxicity observed. Complete remission was achieved by 6 out of 6 patients with bone marrow blasts greater than 5% at enrollment, with 5 of these patients also achieving minimal residual disease (MRD)-negative status.

The study concludes that the FasTCAR™ technology enables the rapid production of dual CAR T-cells with a younger and less exhausted phenotype, which exhibit more potent efficacy in preclinical models. Clinical data supports the safety and efficacy of GC022F in treating CD19+CD22+ B-ALL patients. Further evaluation with additional patients and extended observation times is necessary to fully assess the potential of the CD19/CD22 dual FasTCAR-T cell product.