Chicago [US]: A small molecule that can control an immune process that is crucial in the development of cancer and autoimmune disorders have been discovered by University of Illinois at Chicago researchers. Their discovery is reported in an Angewandte Chemie paper titled "Discovery of the First Selective Nanomolar Inhibitors of ERAP2 by Kinetic Target-Guided Synthesis."
They first investigated how the immune system functions and why some diseases can be resistant to treatments before discovering the molecule, an enzyme inhibitor. "Tumors have the ability to present cell-surface markers in the form of non-self peptide antigens, or neoantigens, which renders them exquisitely sensitive to recognition and elimination by T-cells, a form of immune cells that kill tumor cells upon recognition of neoantigens," said study corresponding author Marlene Bouvier, UIC professor of microbiology and immunology at the College of Medicine.
"The visibility of a tumor to T-cells is therefore a critical aspect of whether a T-cell based immunotherapy treatment will be successful. Unfortunately, most tumors have low expression levels of neoantigens on their surfaces and, consequently, are resistant to immunotherapies." Endoplasmic reticulum aminopeptidases 1 and 2, also known as ERAP1 and ERAP2, are proteins that are in charge of trimming and over-trimming peptide antigens and neoantigens inside of cells. For the study, the team examined these enzymes.