Selective Inhibition of T Cell Tolerance as a Means of Enhancing Tumor Vaccines in a Mouse Model of Breast Cancer
Final rept. 15 May 2003-14 May 2006
JOHNS HOPKINS UNIV BALTIMORE MD
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To determine if the addition of Go6976 to vaccine protocols will inhibit neu specific tolerance and enhance immunotherapy for breast cancer. Scope In the Her-2neu model of spontaneous breast cancer the immune system of these transgenic mice are tolerant to the neu protein. While immunity to neu can be demonstrated in the neu-transgenic mice partial breaking of tolerance, this immunity is inadequate to prevent the spontaneous development of tumors and to prevent death from tumor challenge. Findings By combining our regimen with a dose of cytoxan we can promote survival of tumor bearing mice when compared with no treatment, vaccine alone or vaccine cytoxan. In particular, this combination is very effective in inhibiting tumor growth in the early period post-tumor challenge. Unfortunately, during the last year efforts to improve long term survival have not been successful. Significance These data support the notion that the novel combination of PKC inhibitor vaccine can enhance the efficacy of tumor vaccines. More work needs to be done to optimized the dosing schedule of this approach.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research