Upregulation of CD19 by low-dose chidamide promotes CAR T cells functionality in B-cell non-Hodgkin lymphoma.

Abstract

B-cell non-Hodgkin lymphoma (B-NHL) is a highly heterogeneous group of lymphopoietic malignancies that account for 85% to 90% of all non-Hodgkin lymphomas. In recent years, CD19 Chimeric antigen receptor T (CAR T) cell immunotherapy has significantly improved the cure rate of B-NHL patients, but there are still some patients who cannot achieve remission after treatment, or relapse after remission. Therefore, it is of great importance to overcome the drug resistance of CD19 CAR T cells after B-NHL treatment and reduce the recurrence rate of CD19 CAR T cells after B-NHL treatment. We found that low concentrations of chidamide did not enhance the ability of CD19 CAR T cells to kill B-NHL cells during and after preparation. B-NHL cells pretreated with chidamide were more likely to be killed by CD19 CAR T cells. CD19 CAR T cells secreted more cytokines (IL-2, TNF-α, and IFN-γ) after co-culture with B-NHL cells pretreated with chidamide. At the same time, the expression of CD19 on B-NHL cell surface was increased by chidamide. In vivo experiments showed that infusion of CD19 CAR T cells after chidamide bridging intervention can enhance the therapeutic effect of B-NHL and prolong the overall survival of mice. This study provides a new direction and theoretical foundation for CD19 CAR T cell therapy in B-NHL.