9. The dual PI3K inhibitor duvelisib potently inhibits cytokine release syndrome while maintaining CAR-T function

Clinical efficacy of CAR-T is limited by toxicities such as Cytokine Release Syndrome (CRS) in over 30% of patients. Using a protein kinase inhibitor library, we identified duvelisib, a novel and selective dual PI3K inhibitor as a potent inhibitor of CRS in vitro and in vivo without attenuating CAR-T function. To study the mechanisms of inhibition of CRS, CART19 (19-28BB?), CD19+ Ramos CBR GFP (CG), and immature dendritic cells (IDC) were co-cultured with duvelisib and ruxolitinib (JAK1/2 inhibitor; a less potent inhibitor of CRS also identified in screen) and submitted for scRNA-seq.

Source: Cancer Genetics and Cytogenetics - November 1, 2022 Category: Genetics & Stem Cells Authors: Parmeshwar Amatya, Alun Carter, Julie Ritchey, Reyka Jayasinghe, Matthew Cooper, Jonathan Pachter, John Dipersio Source Type: research