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 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.
Soergel
S A
SA
Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison 53706, USA.
MacEwen
E G
EG
Vail
D M
DM
Potter
D M
DM
Sondel
P M
PM
Helfand
S C
SC
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000951:Antigens, Neoplasm / Q000276:immunology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D003601:Cytotoxicity Tests, Immunologic; D004285:Dogs; D004306:Dose-Response Relationship, Immunologic; D016233:Immunotherapy, Active; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008175:Lung Neoplasms / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D008262:Macrophage Activation / Q000276:immunology*; D016676:Macrophages, Alveolar / Q000276:immunology*; D008545:Melanoma / Q000276:immunology / Q000556:secondary / Q000628:therapy*; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D007371:Interferon-gamma