Despite excellent surgical technique and advances in the use of chemotherapy and radiation, human patients with oral melanoma only have a 5 year survival of around 15-20 percent. The central hypothesis of this application is that following surgical excision of primary oral melanoma, administration of autologous tumor cell vaccine (ATCV) expressing human granulocyte-macrophage colony stimulating factor (hGM-CSF), will result in improved disease free intervals and overall survival time compared to surgery alone. We will test this hypothesis using spontaneous oral melanoma in the dog model. This tumor mimics the human tumor with respect to pathology, biologic behavior, metastatic pattern, and overall poor prognosis following conventional therapy. Furthermore, we have exciting preliminary data showing safety, biologic activity, and significant antitumor activity using ATCV in the dog model. To accomplish our objectives we will pursue 4 specific aims: (1) determine if ATCV provides a survival advantage in a surgical adjuvant randomized trial; (2) determine if ATVC-treated dogs develop a Th1 inflammatory response to the vaccine; (3) determine if vaccination induces a specific immune response as measured by lymphocyte cytotoxicity assays, proliferation assays, and DTH using autologous tumor cells; and (4) determine if there is a humoral immune response to the primary tumor and autologous tumor cells. At the completion of this research project, we expect to have determined the antitumor activity of hGM-CSF ATCV as an adjuvant to surgical excision. Furthermore, we expect to have a better understanding of the mechanism of action of genetically-modified ATCV.
| Alexander, A N; Huelsmeyer, M K; Mitzey, Ann et al. (2006) Development of an allogeneic whole-cell tumor vaccine expressing xenogeneic gp100 and its implementation in a phase II clinical trial in canine patients with malignant melanoma. Cancer Immunol Immunother 55:433-42 |
