POTENTIAL TO INVOLVE MULTIPLE EFFECTOR-CELLS WITH HUMAN RECOMBINANT INTERLEUKIN-2 AND ANTIGANGLIOSIDE MONOCLONAL-ANTIBODIES IN A CANINE MALIGNANT-MELANOMA IMMUNOTHERAPY MODEL

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 a ntibodies (Mabs). The purpose of this study was to investigate express ion and targeting of gangliosides on canine melanoma. Using immunohist ochemical methods, we analyzed the expression of disialogangliosides G D2 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 m ouse-human chimera, ch 14.18) to mediate antibody-dependent cellular c ytotoxicity (ADCC) in vitro against a canine malignant melanoma cell l ine with human recombinant interleukin-2 (IL-2) activated canine perip heral blood lymphocytes (PBL), or canine neutrophil effector cells. Ou r data show that Mabs 14.G2a and R24 recognized fresh frozen canine or al melanoma. Mabs 14.G2a or ch 14.18, or IL-2, potentiated lysis of th e canine malignant melanoma cell line by canine PBL. The killing effec t observed using the combination of either Mab with IL-2 was additive. Mab 14.G2a mediated potent ADCC of canine melanoma by canine neutroph ils. These studies indicate that disialogangliosides are expressed on fresh canine melanoma cells. Mabs reactive with these antigens can tar get and trigger tumor killing by multiple canine effector populations and IL-2 can potentiate these effects by canine lymphocytes. Thus, can ine oral malignant melanoma, a spontaneously occurring, metastatic can cer in the dog, may be a relevant animal model to investigate combinat ion immunotherapy using antitumor Mab and IL-2.