Priming Leukemia with 5-Azacytidine Enhances CAR T Cell Therapy.

ABSTRACT:

Purpose

Despite the success of chimeric antigen receptor (CAR) T cells in clinical studies, a significant proportion of responding patients eventually relapsed, with the latter correlating with low CAR T cell expansion and persistence.

Methods and results

Using patient-derived xenograft (PDX) mouse models of CD19⁺ B cell acute lymphoblastic leukemia (B-ALL), we show that priming leukemia-bearing mice with 5-azacytidine (AZA) enhances CAR T cell therapy. AZA given 1 day prior to CAR T cell infusion delayed leukemia growth and promoted CAR T cell expansion and effector function. Priming leukemia cells with AZA increased CAR T cell/target cell conjugation and target cell killing, promoted CAR T cell divisions and expanded IFNγ⁺ effector T cells in co-cultu

SUBMITTER: Xu N 

PROVIDER: S-EPMC8091475 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature