Modulation of proteinase receptor 2: a novel target for cancer immunotherapy

Treatments empowering patient’s own immune system (immunotherapy) have revolutionized cancer treatment this last decade, showing substantial clinical activity in different tumor types. However, 60% of cancer patients still fail to respond to immunotherapy and other standard of care. Our laboratory recently identified the proteinase receptor 2as a new target to overcome immunotherapy resistance. We propose to investigate the therapeutic potential of this receptor for cancer immunotherapy.

Design and development of pharmacological chaperones to restore function to MC4R mutants responsible for severe early-onset obesity.

"Melanocortin 4 receptor (MC4R) is a is a G protein-coupled receptor (GPCR) and key regulator of energy homeostasis. MC4R mutations represent the largest monogenic cause of obesity, resulting mainly from receptor misfolding and intracellular retention by the cellular quality control system. The efficacy of several lead compounds on restoring the cell surface expression and function of mutated MC4R has already been tested in our laboratory. One compounds restored the anorexic response to MC4R agonist in a KI mice model.