Malignant brain tumors arise in more than 40,000 people in the United States each year. About half are primary and the remainder are metastatic. Brain metastasis is frequent in patients suffering from many systemic malignancies including lung, breast melanoma, lymphoma, and colon cancers. Brain tumors are the second most common cause of cancer-related death in people up to the age of 35, with a slight peak of incidence in occurrence among children between the ages of 6 and 9. Current standard of care of patients with malignant brain tumor includes surgery, radiation therapy, and possibly chemotherapy. Unfortunately, despite numerous combined modality treatment trials over the part 2 decades, patient survival is still numbered in months. The experiments proposed in this application are designed to study a novel unconventional strategy for the treatment of malignant brain tumors based on gene/immune therapy. The investigators have produced successful vaccination against malignant brain tumors in animals by immunization into the brain with a live growth-competent tumor vaccine. In this animal model, intra-cerebrally-implanted malignant glial cells, genetically- modified to secrete interferon-gamma, elicit tumor rejection and specific protective systemic anti-tumor immunity. This biologic response is associated with activation of microglia throughout the brain and enhanced infiltration by CD4, CD8, and natural killer cells. The proposed research is intended to: 1) conduct pre- clinical experimentation of gene/immune therapy of established malignant brain tumors in animals by gene transfer of interferon gamma and interleukin 12, and 2) elucidate the basic principles of vaccination in the brain. The concept of anti-tumor immunization by delivering a vaccine directly into the brain, an organ thought to be immunologically-privileged, is novel. Furthermore, this research is important not only because positive results will lead to immediate phase I clinical trials in patients with either primary or metastatic brain tumors, but also because it will shed light on the principle of immunotherapy against central-nervous-system tumors.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA081367-01
Application #
2837826
Study Section
Experimental Immunology Study Section (EI)
Program Officer
Hecht, Toby T
Project Start
1999-04-08
Project End
2002-03-31
Budget Start
1999-04-08
Budget End
2000-03-31
Support Year
1
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Neurology
Type
Schools of Medicine
DUNS #
City
Dallas
State
TX
Country
United States
Zip Code
75390
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