Strategic Manipulation of Turmor Antigens to Enhance Immunogenicity
Abstract
Systemic chemotherapy including high dose chemotherapy with autologous stem cell rescue frequently induces responses in women with metastatic breast cancer. In spite of the substantial response rate, most women will have recurrent disease. Recurrence and progression of breast cancer is thought to be due to chemotherapy resistant tumor cells. The immune system including cytolytic T lymphocytes can effectively target and kill chemotherapy resistant tumor cells. The findings that tumor associate antigens, particularly antigens derived from the Her-2/neu oncogene can be recognized in breast cancer suggests that strategies to enhance immune recognition of these tumor antigens may provide a therapeutic benefit. Recent studies indicate that the N-terminal flanking region of the peptide from the invariant chain termed CLIP has superagonistic properties that can augment the immune response to nominal peptide antigens. The central hypothesis of this proposal is that the N-terminal flanking region of CLIP can augment the immunogenicity of cryptic "self" epitopes from tumor associated antigens such as Her- 2/neu. Chimeric constructs of Her-2/neu peptide with the N-terminal flanking region of CLIP will be utilized to determine whether vaccination with this construct can augment the immune response to this antigen. Analysis of the immune response to these peptides will include antibody production, CD4+ and CD8+ dependent cellular immunity (lymphoproliferation, cytokine production) and cytolytic T cell function.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2000
- Accession Number
- ADA386849
Entities
People
- Allan D. Hess
Organizations
- Johns Hopkins University