Synergistic effect of ibrutinib and CD19 CAR-T cells on Raji cells in vivo and in vitro

Abstract Background Ibrutinib might improve the efficacy of CD19 CAR-T cell therapy in chronic lymphocytic leukemia (CLL). We expect to study the possibility and mechanism of synergistic effect of ibrutinib and CAR-T cells in other types of lymphoma. Methods We selected the CD19 CAR-T cells of a patient who failed in this therapy and a dose of 8 mg/kg/day ibrutinib to study the synergistic effect. Subcutaneous and tail vein tumorigenic mice were established with Raji cells. The differences of the synergistic effect between these two models were compared by bioluminescence imaging (BLI) monitoring and flow cytometry (FCM). Then the expression of STAT-3 signaling pathway was assessed by western blot analysis. Results The expression of PD-L1 was 0.23±0.06% in Raji cells. In subcutaneous tumorigenic model, the luciferase signal was reduced significantly in the ibrutinib combined with CD19 CAR-T cell group. The proportion of CD19 CAR-T cells was higher in the polytherapy group than that of the CAR-T cell monotherapy group. But we didn't get analogous synergistic effect in tail vein tumorigenic model. There was no difference between the STAT-3 signaling pathway expression in residual tumor cells with or without ibrutinib. Conclusions Our result might indicate that no IL-10/STAT-3/PD-L1 pathway were involved in the synergistic effect. Then some other mechanism about tumor microenvironment might be a possible target for ibrutinib. We expect our results provide evidence for the use of ibrutinib in polytherapy to other types of B cell lymphoma.