The Immunotherapeutic Potential of Activated Canine Alveolar Macrophages and Antitumor Monoclonal Antibodies in Metastatic Canine Melanoma
Overview
Affiliations
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.
A Review of Immunotherapeutic Strategies in Canine Malignant Melanoma.
Almela R, Anson A Vet Sci. 2019; 6(1).
PMID: 30759787 PMC: 6466282. DOI: 10.3390/vetsci6010015.
Generation of a canine anti-EGFR (ErbB-1) antibody for passive immunotherapy in dog cancer patients.
Singer J, Fazekas J, Wang W, Weichselbaumer M, Matz M, Mader A Mol Cancer Ther. 2014; 13(7):1777-1790.
PMID: 24755200 PMC: 4174294. DOI: 10.1158/1535-7163.MCT-13-0288.
Alexander A, Huelsmeyer M, Mitzey A, Dubielzig R, Kurzman I, MacEwen E Cancer Immunol Immunother. 2005; 55(4):433-42.
PMID: 15965647 PMC: 11031070. DOI: 10.1007/s00262-005-0025-6.