Selective Inhibition of T Cell Tolerance as a Means of Enhancing Tumor Vaccines in a Mouse Model of Breast Cancer
Abstract
This report of the purpose is to determine if the addition of Go6976 to vaccine protocols will inhibit the re-induction of neu specific tolerance and thus facilitate immune mediated protection against breast cancer. 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 in terms of preventing the spontaneous development of tumors and preventing death from tumor challenge. Our experiments involve concomitantly treating mice with the PKC inhibitor Co6976 during tumor vaccine therapy in order to prevent tolerance induction and enhance immunotherapy. In initial experiments death from tumor was delayed by approximately 1 week in treated mice versus untreated controls. Likewise, in a second experiment non of the untreated mice (0/10) demonstrated evidence of neu-specific T cell responses, while 1/10 treated mice demonstrated neu-specific T cells. Importantly, the responder mouse had no evidence of tumor. These initial experiments while not dramatic suggest that the administration of Go6979 can impact immunotherapy. With these initial studies as a guide the major focus now is optimizing the delivery of the drug and vaccine.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2004
- Accession Number
- ADA427665
Entities
People
- Jonathan D. Powell
Organizations
- Johns Hopkins University