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Potential to involve multiple effector cells with human recombinant interleukin-2 and antiganglioside monoclonal antibodies in a canine malignant melanoma immunotherapy model.
|Title||Potential to involve multiple effector cells with human recombinant interleukin-2 and antiganglioside monoclonal antibodies in a canine malignant melanoma immunotherapy model.|
|Publication Type||Journal Article|
|Year of Publication||1994|
|Authors||Helfand SC, Soergel SA, Donner RL, Gan J, Hank JA, Lindstrom MJ, Sondel PM|
|Journal||Journal of immunotherapy with emphasis on tumor immunology : official journal of the Society for Biological Therapy|
|Date Published||1994 Oct|
|Keywords||Animals, Antibodies, Monoclonal, Antibody-Dependent Cell Cytotoxicity, Cytotoxicity Tests, Immunologic, Disease Models, Animal, Dog Diseases, Dogs, Flow Cytometry, Gangliosides, Interleukin-2, Leukocytes, Melanoma, Mouth Neoplasms, Recombinant Proteins, Tumor Cells, Cultured|
Human tumors originating from neuroectodermal cells such as malignant melanoma and neuroblastoma express high levels of disialogangliosides GD2 and GD3, making these antigens ideal for targeting by monoclonal antibodies (Mabs). The purpose of this study was to investigate expression and targeting of gangliosides on canine melanoma. Using immunohistochemical methods, we analyzed the expression of disialogangliosides GD2 and GD3 on canine oral malignant melanomas with murine Mabs 14.G2a and R24 that recognize GD2 and GD3 disialogangliosides, respectively, on human tumors. We also assessed the ability of Mab 14.G2a (and its mouse-human chimera, ch 14.18) to mediate antibody-dependent cellular cytotoxicity (ADCC) in vitro against a canine malignant melanoma cell line with human recombinant interleukin-2 (IL-2) activated canine peripheral blood lymphocytes (PBL), or canine neutrophil effector cells. Our data show that Mabs 14.G2a and R24 recognized fresh frozen canine oral melanoma. Mabs 14.G2a or ch 14.18, or IL-2, potentiated lysis of the canine malignant melanoma cell line by canine PBL. The killing effect observed using the combination of either Mab with IL-2 was additive. Mab 14.G2a mediated potent ADCC of canine melanoma by canine neutrophils. These studies indicate that disialogangliosides are expressed on fresh canine melanoma cells. Mabs reactive with these antigens can target and trigger tumor killing by multiple canine effector populations and IL-2 can potentiate these effects by canine lymphocytes. Thus, canine oral malignant melanoma, a spontaneously occurring, metastatic cancer in the dog, may be a relevant animal model to investigate combination immunotherapy using antitumor Mab and IL-2.
|Alternate Journal||J Immunother Emphasis Tumor Immunol|