The high-affinity IgG receptor, FcγRI, plays a central role in antibody therapy of experimental melanoma

We examined the role of Fc gamma R in antibody therapy of metastatic melanoma in wild-type and different Fc gamma R knockout 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 Fc gamma R knock-out mice revealed the high-affinity IgG receptor, Fc gamma RI (CD64), to represent the central Fc gamma R for TA99-induced antitumor effects. The potential of immunemodulating 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 Fc gamma RI.