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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE013137-04
Application #
6523870
Study Section
Special Emphasis Panel (ZDE1-GH (03))
Program Officer
Mangan, Dennis F
Project Start
1999-09-24
Project End
2003-08-31
Budget Start
2002-09-01
Budget End
2003-08-31
Support Year
4
Fiscal Year
2002
Total Cost
$108,704
Indirect Cost
Name
University of Wisconsin Madison
Department
Other Basic Sciences
Type
Schools of Veterinary Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715