Modulation of T-Cell Activation in an Experimental Model of Mammary Carcinoma.
Abstract
One of the major goals of tumor immunotherapy is the induction of tumor-specific T cell responses that will be effective at eradicating disseminated tumors. The studies described in this update take advantage of our current knowledge of T cell activation and inhibitory signals. Using a transplantable mammary carcinoma, we demonstrated that blockade of inhibitory signals mediated by CTLA-4 using a monoclonal antibody synergizes with a cell-based vaccine to promote regression of the unmanipulated tumor in a T cell-dependent mechanism. Our recent studies have taken the information gained using this model and applied it to two models of primary carcinogenesis. Using an N-methyl- N-nitrosourea-induced model of mammary carcinogenesis, we have observed that active rejection of a genetically-modified tumor line induces protection against tumor development whereas vaccination in combination with anti-CTLA-4 did not confer similar immunity. In addition, using a transgenic model of prostate cancer, we have demonstrated that vaccination with a genetically-modified tumor line in combination with anti-CTLA-4 reduces tumor incidence, prolongs survival, and induces a strong intraprostatic inflammatory response. These results are discussed in the context of the goals of the proposal and additional experiments to be performed in the final year are described.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1998
- Accession Number
- ADA360025
Entities
People
- Arthur A. Hurwitz
Organizations
- University of California, Berkeley