Description:
The current state of arts:
Heat shock protein (Hsp) 90 inhibition is a potential mechanism for enhancing cancer immunotherapy.
The problems with the current arts:
However, none of the first-generation Hsp90 inhibitors and newly developed inhibitors have been FDA approved for cancer immunotherapy. It is urgent to identify an efficacious Hsp90 inhibitor that does not activate anti-apoptotic proteins.
The advantage of our invention:
AU researchers have identified the cyclohexadepsipeptide Enniatin A (EnnA), a natural compound as a novel inhibitor of Hsp90 chaperoning machine, based on the progesterone receptor, an established physiological client protein of Hsp90. At the molecular level, EnnA reduces the protein levels of two key mediators of tumor-induced immune tolerance: programmed cell death ligand-1 (PDL-1) and indolamine 2,3 dioxygenase (IDO). In xenograft mice, EnnA induces a powerful T cell-mediated immune response, resulting in highly efficient tumor killing and long-term memory against the primary tumor. Therefore, EnnA is promising cancer immunotherapy to complement current checkpoint inhibitors.
AURI # 2017-040
IP status: US non-provisional 16/180,203
Reference: https://cancerres.aacrjournals.org/content/79/13_Supplement/12.short