Monocyte-mediated lysis of acute myeloid leukemia cells in the presence of the bispecific antibody 251 x 22 (anti-CD33 x anti-CD64).

摘要: Immunotherapy using bispecific antibodies (BsAb) to direct immune effector cells toward target tumor has been shown be effective in a number of studies. Several trigger molecules have characterized. Among them, FcgammaRI appears play an important role antibody-dependent cellular cytotoxicity. It is expressed mainly on monocytes, macrophages, and neutrophils under certain clinical situations. The expression can regulated by variety cytokines, primarily IFN-gamma. Recent studies that granulocyte-colony-stimulating factor (G-CSF) granulocyte-macrophage-colony stimulating (GM-CSF) increase the FcgammaRI-positive circulating after vivo infusion, greatly enhance cytotoxic activity neutrophils. CD33 glycoprotein cell surface mature myeloid progenitor cells, leukemic blasts, but not earliest hematopoietic other normal tissues. Herein, we report construction BsAb, 251 x 22, conjugating anti-CD33 mAb (mAb 251) anti-FcgammaRI 22). BsAb 22 capable enhancing cytotoxicity several leukemia lines cytokine-activated monocytes. Our data also show G-CSF- GM-CSF-stimulated monocytes mediate comparable IFN-gamma-stimulated 24-h vitro incubation with G-CSF GM-CSF was increased, although significantly. Prolonged for 48 h significantly increased expression. Because humanized are available, because used widely patients chemotherapy stimulate recovery hematopoiesis, additional development this project feasible. A comprised could application treatment leukemia, especially management minimal residual disease.