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

TitleThe immunotherapeutic potential of activated canine alveolar macrophages and antitumor monoclonal antibodies in metastatic canine melanoma.
Publication TypeJournal Article
Year of Publication1999
AuthorsSoergel SA, MacEwen EG, Vail DM, Potter DM, Sondel PM, Helfand SC
JournalJournal of immunotherapy (Hagerstown, Md. : 1997)
Volume22
Issue5
Pagination443-53
Date Published1999 Sep
ISSN1524-9557
KeywordsAdjuvants, Immunologic, Animals, Antibodies, Monoclonal, Antigens, Neoplasm, Antineoplastic Agents, Cytotoxicity Tests, Immunologic, Dogs, Dose-Response Relationship, Immunologic, Immunotherapy, Active, Interferon-gamma, Recombinant, Lipopolysaccharides, Lung Neoplasms, Macrophage Activation, Macrophages, Alveolar, Melanoma, Tumor Cells, Cultured
Abstract

A variety of immune cell activators can enhance the cytotoxic effects of monocytes/macrophages including interferon-gamma (IFN-gamma) and muramyl peptides, which are under investigation for cancer therapy in humans and dogs. Pulmonary alveolar macrophages (PAMs) in particular, are strategically located within the lung and provide a potential defense against cancer cells metastatic to the lung. For this reason, we examined the in vitro cytotoxic potential 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, significantly enhanced the cytotoxicity of canine melanoma mediated by canine PAMs. Further, the cytotoxicity mediated by recombinant canine IFN-gamma-activated canine PAMs, in combination with anti-GD2 ganglioside mAb 14.G2a, enhanced melanoma cytotoxicity above that seen with mAb 14.G2a alone. This documentation of antibody-dependent cellular cytotoxicity mediated by activated PAMs suggests that activation and targeting of resident pulmonary immune cells be pursued as a means to control pulmonary metastases.

Alternate JournalJ. Immunother.