Fig. 1

Enhancement of anti-tumor immunity by antibody-targeted IFN-α in B cell malignancies. Antibody-IFN-α fusion proteins are given by intravenous administration. The delivery of concentrated quantities of IFN-α to malignant sites is facilitated by tumor specific mAbs. Three potentially important mechanisms used by antibody-IFN-α fusion proteins to kill targeted tumor cells are: (1) IFN-αR mediated signals, i.e., IFN-α binds to membrane receptor IFN-αR expressed on tumor cells and activates downstream pathways to induce apoptosis; (2) IFN-α internalization, i.e., after mAb-IFN-α fusion proteins are internalized, IFN-α is released within cancer cells; (3) enhancing Fc receptor mediated ADCC, i.e., IFN-α augments ADCC exerted by mAbs through binding to the membrane receptor IFN-αR expressed on effector cells. E effector cells including NK cells, γδ T cells, macrophages and dendritic cells, B malignant B cells, IFN interferon, sIFN-αR soluble interferon alpha receptor, mAb monoclonal antibody, ADCC antibody-dependent cell-mediated cytotoxicity