Recombinant Vaccine Strategies for Breast Cancer Prevention
Abstract
Exciting new findings in autoimmune disease and cancer have led to the realization that a large set of antigenic determinants of the self have not induced self-tolerance. These peptide determinants could provide target structures for autoimmune attack as well as antitumor immune responses. We hypothesized that vaccine strategies can be devised that specifically generate an immune response against breast ductal epithelial cells. Since the overwhelming majority of breast tumors arise in these cells, destroying these cells prior to the development of neoplasia will effectively prevent cancer. We are attempting to augment the immune response to the breast-specific antigen, HER-2/neu, which is expressed by mammary tissue in HER-2/neu transgenic mice prior to mammary tumor development, by enhancing the T cell response using selected vectors that may alter antigen processing and T cell activation, thereby influencing antigen-specific immunity. We have evaluated vaccinia constructs that express antigen alone or together with co-stimulatory molecules, to determine if immunity can be further enhanced. In our preliminary studies, we have found that this vaccinia approach is superior to vaccination with plasmid DNA. We are currently exploring additional methods of enhancing the potency of this vaccine approach, including testing a fusion protein that enhances the induction of helper T cell responses, and testing the vaccine in combination with other recently identified T cell activating signals such as CD4O, OX4O, and anti-CTLA-4. This study will provide a paradigm for novel vaccine approaches to breast cancer prevention.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1999
- Accession Number
- ADA381767
Entities
People
- Elizabeth M. Jaffee
Organizations
- Johns Hopkins University