Maximizing Immune Response to Carbohydrate Antigens on Breast Tumors
Abstract
Tumor antigens are autologous antigens and thus are weakly immunogenic. Unresponsiveness appears to be related to suppression of antigen specific helper T cell function which can be overcome by providing heterologous help. Carbohydrates are richly expressed on the surface of many cancers, at frequencies higher than oncogene products. Consequently, tumor associated carbohydrate antigens, are in principle, excellent targets for immunotherapy. However, carbohydrates are generally poor at eliciting effective antibody responses and rarely provide target epitopes for CTL because of their T cell-independent nature. The major objective of this application is to examine ways to maximize the tumor-protective immunity directed to carbohydrate antigens expressed on breast tumors. Towards this end we are developing peptide mimotopes of tumor associated carbohydrate antigens as they are T cell dependent antigens. In our progress to date we have shown that 1.) We observed that transfection with Fut 3 changes the expression profile of E selectin reactivity. 2) We defined potential peptide mimotopes for targeting 4T1 cells in vivo. 3) We observed that immunization with DNA induced IgM antibodies reactive with 4T1 cells. 4) We observed that DNA administration of 4T1-tumor bearing animal temporarily reduces the burden of tumor. 5) DNA administration of the 107 peptide significantly increases survival rate of animals. 6) We observed that administration of 107 DNA inhibits liver metastases.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2004
- Accession Number
- ADA435539
Entities
People
- Thomas Kieber-emmons
Organizations
- University of Arkansas for Medical Sciences