FC-RECEPTORS ARE REQUIRED IN PASSIVE AND ACTIVE IMMUNITY TO MELANOMA

Effective tumor immunity requires recognition of tumor cells coupled w ith the activation of host effector responses, Fc receptor (FcR) gamma (-/-) mice, which lack the activating Fc gamma R types I and III, did not demonstrate protective timer immunity in models of passive and act ive immunization against a relevant tumor differentiation antigen, the brown locus protein gp75. In wild-type mice, passive immunization wit h mAb against gp75 or active immunization against gp75 prevented the d evelopment of lung metastases, This protective response was completely abolished in FcR gamma-deficient mice. Immune responses were intact i n gamma(-/-) mice because IgG titers against gp75 develop normally in gamma(-/-) mice immunized with gp75, However, uncoupling of the Fc gam ma R effector pathway from antibody recognition of tumor antigens resu lted in a loss of protection against tumor challenge, These data demon strate an unexpected and critical role for FcRs in mediating tumor cyt otoxicity in vivo and suggest that enhancement of Fc gamma R-mediated antibody-dependent cellular cytotoxicity by inflammatory cells is a ke y step in the development of effective tumor immunotherapeutics.