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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.
- Source :
-
Journal of immunotherapy with emphasis on tumor immunology : official journal of the Society for Biological Therapy [J Immunother Emphasis Tumor Immunol] 1994 Oct; Vol. 16 (3), pp. 188-97. - Publication Year :
- 1994
-
Abstract
- 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.
- Subjects :
- Animals
Antibodies, Monoclonal therapeutic use
Antibody-Dependent Cell Cytotoxicity drug effects
Antibody-Dependent Cell Cytotoxicity immunology
Cytotoxicity Tests, Immunologic
Disease Models, Animal
Dog Diseases
Dogs
Flow Cytometry
Interleukin-2 therapeutic use
Leukocytes immunology
Melanoma immunology
Melanoma veterinary
Mouth Neoplasms veterinary
Recombinant Proteins immunology
Tumor Cells, Cultured
Gangliosides immunology
Melanoma therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1067-5582
- Volume :
- 16
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of immunotherapy with emphasis on tumor immunology : official journal of the Society for Biological Therapy
- Publication Type :
- Academic Journal
- Accession number :
- 7834118
- Full Text :
- https://doi.org/10.1097/00002371-199410000-00003