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 attempted 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, thereby influencing antigen-specific immunity. We have evaluated DNA vectors that express antigen alone or together with the cytokine, GM-CSF, to determine if this immunity can be further enhanced. An intramuscular approach was compared with gene gun delivery. Due to suboptimal results, we then explored vaccinia vectors containing the HER- 2/neu gene with or without co-stimulatory molecules. We found that vaccinia containing the antigen plus the UM-CSF gene was most potent in delaying the development of spontaneous mammary tumors. We have found that gene gun delivery is superior for enhancing antitumor immunity. Two additional findings that arose from these studies include: 1) The requirement for vaccine induced antibody responses; the requirement for vaccination early prior to significant overexpression of the antigen. We will follow up on these findings ultimatel to design the 0ptimal vaccine for the prevention of breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2000
- Accession Number
- ADA391356
Entities
People
- Elizabeth M. Jaffee
Organizations
- Johns Hopkins University