Rationally designed inhibitor targeting antigen-trimming aminopeptidases enhances antigen presentation and cytotoxic T-cell responses
Abstract
The human immune system fights disease by eradicating sick cells after first recognizing that they are infected or cancerous. This is achieved by specialized cells that detect on the surface of other cells small molecules called antigenic peptides. Pathogens and cancer can evade the immune system by stopping the generation of antigenic peptides. We designed, synthesized and evaluated artificial small molecules that can effectively block a group of enzymes that are key for the production or destruction of antigenic peptides. We show that these compounds can enhance the generation of antigenic peptides in cells and enhance the immune system reaction toward cancer. Inhibitors of this kind may provide a new approach to coax the immune system into recognizing and eliminating cancer cells.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- December 2013
- DOI:
- 10.1073/pnas.1309781110
- Bibcode:
- 2013PNAS..11019890Z