SUMOylation inhibition potentiates CAR T activity against Multiple Myeloma (scRNA-Seq)

Chimeric antigen receptor (CAR)-T cell therapy has shown remarkable clinical efficacy against hematologic malignancies; however, tumor relapse occurs commonly due to T cell dysfunction presenting as exhaustion and loss of effector function. Here, we identified SUMOylation inhibition promoted T cell effector function and prevented T cell exhaustion. Combination of SUMO E1 inhibitor TAK-981, significantly potentiated CAR T cell anti-tumor activity and improved persistence of CAR-presenting T cells in vivo, presenting a potent novel therapeutic approach. Overall design: MM1S-Luc cells were intravenously (i.v.) injected to 6-10-week old NSG mice via tail vein (2x106 cells/mouse). After 5 days, tumor xenografts were confirmed by bioluminescence imaging. Mice were injected intravenously with dosed 2.5 × 105BCMA-CAR T cells followed by treatment with TAK-981 (7.5 mg/kg, intraperitoneally (i.p.) twice per week, BIW) or Vehicle (Veh) for 2 weeks. Bone marrow mononuclear cells were isolated and stained with human CD45 antibody. Total human T cells were sorted by gating GFP-/DAPI-/human CD45+.