Selective Inhibition of T Cell Tolerance as a Means of Enhancing Tumor Vaccines in a Mouse Model of Breast Cancer

摘要

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-2/neu 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.