EpCAM Inhibition Sensitizes Chemoresistant Leukemia to Immune Surveillance

Menée in vitro et à l'aide de modèles murins, cette étude met en évidence la surexpression de la protéine d'adhérence cellulaire EpCAM dans les cellules de leucémie myéloïde aiguë résistantes à la chimiothérapie, puis montre que l'inhibition d'EpCAM, à l'aide d'anticorps, favorise la destruction de ces cellules par le système immunitaire

Résumé en anglais

The lack of effective tumor-associated antigens restricts the development of targeted therapies against myeloid leukemia. In this study, we compared gene expression patterns of acute myeloid leukemia (AML) and normal bone marrow samples and found that epithelial cell adhesion molecule (EpCAM) is frequently overexpressed in patients with AML, with EpCAM+ leukemic cells exhibiting enhanced chemoresistance and oncogenesis. The chemotherapeutic resistance of EpCAM-positive leukemic cells is a consequence of increased WNT5B signaling. Furthermore, we generated EpCAM antibodies that enabled phagocytosis or cytotoxicity of AML cells by macrophage or natural killer cells, respectively. Finally, EpCAM antibody treatment depleted AML in subcutaneous, disseminated, and intramedullary engrafted mice. In summary, EpCAM exhibits promise as a novel target for the treatment of leukemia. Cancer Res; 77(2); 1–12. ©2016 AACR.