Work

mRNA-dendritic cell antigen vaccine potentiates CD38 CAR-T Cell therapy for relapsed/refractory acute myeloid leukemia

Year: 2026

Type: article

Abstract: Background: Chimeric antigen receptor (CAR) T-cell therapy has emerged as a promising strategy for management of relapsed/refractory acute myeloid leukemia (R/R AML). Safety and preliminary activity of CD38-targeted CAR-T cells in R/R AML were demonstrated in our prior study; however, relapse with CD38-positive blasts persisted, which was partly associated with insufficient effector function and persistence of CAR-T cells. Given that CAR-T cell hypofunction is promoted by inadequate antigen stimulation, a lipid nanoparticle-delivered CD38 mRNA vaccine was developed to enhance CD38 CAR-T cell efficacy via exogenous antigen presentation. Methods: antitumor efficacy was validated in a THP-1 AML xenograft model. Results: , vaccine administration promoted CAR-T cell expansion, improved tumor control, and prolonged survival. Conclusions: CD38 mRNA-LNP vaccine can efficiently deliver pulsatile CD38 antigen to splenic APCs and augment the proliferation, effector function, and persistence of CD38 CAR-T cells through dual CAR and costimulatory signaling, which may represent a promising strategy to overcome CAR-T cell dysfunction in R/R AML.

Source: Theranostics

DOI: 10.7150/thno.139339