Decitabine enhances antibody-dependent effects of Daratumumab immunotherapy in acute lymphoblastic leukemia models

Résumé fourni par la source

Current treatment of acute lymphoblastic leukemia (ALL) involves intensive chemotherapy with severe side effects. Options for relapsed/refractory (r/r) cases are limited, particularly in T-ALL, and antibody therapy is a promising alternative. CD38, expressed on both B-cell precursor (BCP)- and T-ALL cells, can be targeted by daratumumab (DARA). The DNA-Methyltransferase1(DNMT1)-inhibitor decitabine (DEC) may enhance CD38 expression on malignant cells, potentially improving DARA efficacy. Therefore, we examined the impact of DEC on the efficacy of DARA in BCP- and T-ALL in vitro. The application of DEC reduced DNMT1-expression and cell viability in BCP- and T-ALL cell lines. CD38 expression under DEC treatment was increased. Moreover, enhanced antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP) were observed in BCP- and T-ALL cell lines after DEC/DARA application. Importantly, DEC/DARA increased ADCP in a variety of patient-derived xenograft (PDX) samples including 4/6 de novo BCP-, 5/5 T-ALL and 5/5 T-PediatricALL PDX samples from r/r disease. Our findings suggest that DEC/DARA is a promising therapy combination in ALL, warranting further investigation in vivo. Publication History Article published online: 10 May 2024 © 2024. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

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