Strategic Manipulation of Tumor Antigens to Enhance Immunogenicity
Abstract
Breast cancer is an increasingly common malignancy representing 30% of all cancers in women. Conventional systemic chemotherapy or high dose chemotherapy with autologous stem cell rescue can induce remissions in a significant number of patients, complete curative responses, however, are uncommon. Nearly all patients die of progressive disease within 3 years. Tumor recurrence and progression are thought to be due to the persistence of chemotherapy-resistant tumor cells. Therefore, strategies that target the resistant tumor cells are required to have a significant impact on the treatment of breast cancer. Recent studies suggest that immunologic approaches may have meaningful clinical impact targeting the chemotherapy resistant tumor cells. In this regard, development of strategies to maximize anti-tumor immunity require augmenting immune mechanisms that specifically recognize tumor-associated antigens. Recent studies suggest that the protein from the Her-2/neu oncogene can act as a tumor-associated antigen in breast cancer. The development of vaccine strategies for breast cancer have focused around the findings that there appears to be active immunity to the Her-2/neu protein. Unfortunately, the immune response is weak and ineffective largely due to the fact that Her-2/neu is a "self" protein with central tolerance to the immunodominant epitopes leaving only cryptic epitopes to be functionally recognized. The principal focus of the current research project is to augment the immunogenicity of the cryptic epitopes from Her-2/neu inducing significant anti-tumor immunity. The central strategy of the proposed work is to strategically modify the cryptic epitope peptides from Her-2/neu with an amino acid sequence from the N-terminal flanking region of the invariant chain peptide termed CLIP.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2002
- Accession Number
- ADA410782
Entities
People
- Allan D. Hess
Organizations
- Johns Hopkins University