Synergistic effects between CD36 monoclonal antibody and cytarabine for treatment of AML.

Acute myeloid leukemia (AML) is a clinically aggressive and genetically heterogeneous hematologic malignancy with persistently poor clinical outcomes, largely due to the resistance to conventional chemotherapeutic agents including cytarabine (Ara-C). Emerging evidence indicates that the upregulation of the scavenger receptor CD36 is associated with AML relapse and drug resistance. In this study, we showed that high expression of CD36 is associated with poor prognosis for patients with AML. We then evaluated the therapeutic potential of a CD36-targeted monoclonal antibody (mAb) in combination with Ara-C, while investigating the molecular mechanisms underlying their synergistic interaction. Our results demonstrated that the combination of anti-CD36 mAb (GZ1) and Ara-C significantly enhanced the sensitivity of AML cells to Ara-C, reduced tumor burden and prolonged survival in both in vitro and in vivo models. Further analysis revealed that the efficacy of mAb GZ1 in combination with Ara-C was dependent on the IgG subtype, with IgG2a and IgG1 exhibiting stronger synergistic effects compared to the IgG3 subclass. Additionally, the study on an Fc-silenced mutant (GZ1 LALAPG) indicated that Fc-mediated functions played a critical role in the enhanced therapeutic effects. These findings highlighted the potential of anti-CD36 mAb in combination with Ara-C as a novel treatment strategy for overcoming drug resistance in AML.