The immunotherapeutic potential of activated canine alveolar macrophages and antitumor monoclonal antibodies in metastatic canine melanoma

A variety of immune cell activators can enhance the cytotoxic effects of mo nocytes/macrophages including interferon-gamma (IFN-gamma) and muramyl pept ides, which are under investigation for cancer therapy in humans and dogs. Pulmonary alveolar macrophages (PAMs) in particular, are strategically loca ted within the lung and provide a potential defense against cancer cells me tastatic to the lung. For this reason, we examined the in vitro cytotoxic p otential of fresh and IFN-gamma-activated PAMs from normal dogs targeted to canine malignant melanoma cells with antiganglioside monoclonal antibodies (mAbs). Antiganglioside mAbs 14.G2a (anti-GD2) and R24 (anti-GD3), both in clinical trials for human neuroectodermal tumors including melanoma, signi ficantly enhanced the cytotoxicity of canine melanoma mediated by canine PA Ms. Further, the cytotoxicity mediated by recombinant canine IFN-gamma-acti vated canine PAMs, in combination with anti-GD2 ganglioside mAb 14.G2a, enh anced melanoma cytotoxicity above that seen with mAb 14.G2a alone. This doc umentation of antibody-dependent cellular cytotoxicity mediated by activate d PAMs suggests that activation and targeting of resident pulmonary immune cells be pursued as a means to control pulmonary metastases.