Advances in conventional therapies are increasingly successful in imaging and sterilizing a brain tumor mass. New approaches are needed to attack the disseminated or infiltrating tumor that remains. This has lead to renewed interest in immunotherapy as an adjunctive mode of treatment. HYPOTHESES 1. In the tumor-bearing brain, intracerebral injection of IFN-g can activate antigen-presenting cells and recruit primed helper T cells. 2 . If the T cells have been primed to tumor antigen, the resulting immune cascade can lead to the destruction of disseminated brain tumor cells.
SPECIFIC AIMS I. WE WILL COMPLETE THE ANALYSIS OF IFN-g-INDUCED CHANGES IN TUMOR-FREE RATS. A. We will determine the dose-response curve for the different IFN-g-mediated effects we have previously defined in unimmunized animals. B. We will compare the IFN-g-mediated changes in rats that have been primed to neural or tumor antigens. II. DO IFN-g TREATMENT AND IMMUNIZATION WORK SYNERGISTICALLY TO CONTROL THE SPREAD OF TUMOR CELLS WITH THE BRAIN? A. We will define the effects of IFN-g treatment alone on tumor spread. B. We will define the effects of [IFN-g treatment + immunization] on tumor spread. C. We will determine whether [IFN-g treatment + immunization to tumor antigen] causes autoimmune disease. METHODS. These studies will be performed in a rat model, in vivo. Stereotactic surgery, histochemistry, immunocytochemistry, and computer-assisted image analysis will be used to establish and analyze the tumor model.
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