The High-Affinity IgG Receptor, FcγRI, Plays a Central Role in Antibody Therapy of Experimental Melanoma

We examined the role of FcγR in antibody therapy of metastatic melanoma in wild-type and different FcγR knock-out mice. Treatment of B16F10-challenged wild-type mice with TA99 antibody specific for the gp75 tumor antigen resulted in a marked decrease in numbers of lung metastases. Treatment of individual FcγR knock-out mice revealed the high-affinity IgG receptor, FcγRI (CD64), to represent the central FcγR for TA99-induced antitumor effects. The potential of immune-modulating agents to further enhance the protective effect induced by monoclonal antibody (mAb) TA99 was examined in combination treatments consisting of mAb TA99 and a TLR-4 agonist, monophosphoryl lipid A (MPL). MPL did potently boost TA99 antibody-induced effects, and combination therapy was, again, found to be dependent on the presence of FcγRI. (Cancer Res 2006; 66(3): 1261-4)