Potential of CD19-CAR T Cell Therapy
Academic clinical data1 published in Nature Medicine in September 2022 demonstrate that a CD19-CAR T cell therapy with a 4-1BB co-stimulatory domain following lymphodepletion with fludarabine and cyclophosphamide induced a clinical remission in five out of five patients with severe, refractory SLE, with up to 17 months of follow up. The safety data demonstrated low risk of cytokine release syndrome (CRS), with grade 1 CRS observed in 3 out of 5 patients, and no observation of neurotoxicity (immune effector cell-associated neurotoxicity syndrome, or ICANS), of any grade. New B cells repopulated within 2-5 months of CAR T infusion in all patients, with no evidence of recurrence of disease or autoantibodies following repopulation.
Our licensed fully human CD19 binder has been clinically evaluated in a dual-CD19xCD22 CAR T under development for B cell leukemia and lymphoma in an investigator-initiated trial in China, where it has shown promising tolerability in ~20 patients. Developed through screening of 100 billion antibody fragments, our CD19 binder was identified and evaluated using FMC63 – the CD19 binder employed in the Nature Medicine study1 – as a benchmark. Compared to FMC63, our binder exhibits similar biologic activity.2 Given its similarity to the CD19-CAR T construct employed in the trial conducted by Professor Georg Schett and his colleagues, including incorporation of a 4-1BB co-stimulatory domain, CABA-201 may have the potential to transform treatment of B cell-mediated autoimmune diseases.
1 Mackensen, Andreas, et al. "Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus." Nature Medicine (2022): 1-9.
2 Dai, Zhenyu, et al. "Development and functional characterization of novel fully human anti‐CD19 chimeric antigen receptors for T‐cell therapy." Journal of Cellular Physiology 236.8 (2021): 5832-5847.
