The goal of this proposal is to study the development of resistance to tumor challenge associated with exposure of animals to tumor cells treated with antisense to IGF-1R RNA. First phase experiments will be performed using a transplantable tumor, C6 rat glioblastoma cells, in a rat model. The initial objective will be to determine if the resistance is caused by the antisense treatment to IGF-1R RNA or by the effect of the treatment, i.e. the cells dying through apoptosis. Apoptosis will be induced in C6 wild-type cells through a variety of methods and these cells will then be tested for their ability to induce resistance to wild-type tumor challenge. In addition, the apoptotic process will be blocked in C6 antisense IGF-1R RNA transfected cells using several different means and these cells will then be tested for their capacity to induce resistance. The mechanism of host resistance will be studied with emphasis on an immune mediated response. The goal of this section is to confirm the hypothesis that resistance to tumor challenge in the C6 antisense model is immune mediated. Cellular and soluble immune components will be assessed for their role in the immune process. The molecules responsible for the induction of resistance will be identified and their mode of action described in particular with reference to the presence of MHC class I and MHC class II molecules. Finally, the results obtained with the C6 rat glioblastoma model will be verified in tumors bearing the glioma-derived mutant EGF receptor variant III to assess the possible utility of the findings for clinical application.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG016522-02
Application #
2909706
Study Section
Subcommittee G - Education (NCI)
Program Officer
Finkelstein, David B
Project Start
1998-05-01
Project End
2001-04-30
Budget Start
1999-05-01
Budget End
2000-04-30
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Thomas Jefferson University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
061197161
City
Philadelphia
State
PA
Country
United States
Zip Code
19107