Selective Inhibition of T Cell Tolerance as a Means of Enhancing Tumor Vaccines in a Mouse Model of Breast Cancer
Abstract
In the Her-2/neu model of spontaneous breast cancer development it is clear that the immune system of these transgenic mice are tolerant to the neu protein (1-3). In this model not only does the overexpression of neu lead to tumorogenesis but the neu protein is the target of both humoral and cellular immunity which prevent tumor-induced death in the non-transgenic mice (1, 4). Indeed, 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. We have demonstrated in vitro that the PKC inhibitor Go6976 has the ability to selectively inhibit TCR induced tolerance induction while only minimally inhibiting T cell activation. We hypothesize that the addition of Go6976 to vaccine protocols will inhibit the reinduction of neu specific tolerance and thus facilitate immune mediated protection against the development of spontaneous breast cancer development and tumor challenge.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2005
- Accession Number
- ADA439190
Entities
People
- Jonathan D. Powell
Organizations
- Johns Hopkins University