Immunity by Hydrophobic Appendage Bearing Antigens
Abstract
The objective of this study was to discover how we can enhance the immunity to tumor Antigens (TA) , in the cancer vaccines. Preventive immunity to cancer in high risk patients or in patients with primary disease is important. The importance rests with a better quality of life and decrease medical costs. To reach the immunopreventive level a vaccine should activate strongly immunity to TA. The strong activation consists in expansion and differentiation of T cells specific for TA. The more effectors expanded by vaccine, the more memory cells. The more differentiated the T cells, the more functional. Our hypothesis is that optimization of the contacts: TA -T cell receptor (TCR) contacts will activate more T cells and it will induce their differentiation. We focused on the side chains of the amino acids in the tumor A. We avoided the changes in the peptide core to minimize cross-reactivity. We discovered that: (1) if side chains are introduced in the amino acid glycine, then the immunogenicity of the TA increase following a bell-shaped plot. (2) if side chains which form the points of contact( link ) TA-T cell receptor are replaced with others which induce electrostatic repulsion, then activation of cells is attenuated. The attenuation minimized death of memory like cells. (3) Increase in distance between TA and TCR with one CH2 group also increase survival of cells activated by TA. (3). Changes in the length and orientation of the N-terminus of the TA also result in increased activation of T cells. The N-terminal variants are effective at low concentrations, but induce death by over-activation. Additional studies were performed towards future goals. The findings of this study were recognized for joint technology elopment and commercialization by MDACC and the Henry Jackson Foundation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2006
- Accession Number
- ADA469767
Entities
People
- Constantin G. Ioannides
Organizations
- The University of Texas MD Anderson Cancer Center