A new immune-oncology drug whose mechanism differs from available cancer immunotherapies, including nivolumab and ipilimumab, has been announced by Dr. Wayne Hancock of University of Pennsylvania School of Medicine, alongside Progenra Inc.

The results, published in EBioMedicine, support a new immune-oncology antitumour strategy by inhibiting USP7, an enzyme that prevents immune activity against cancer in addition to supporting the growth of cancer cells.

The authors describe in the paper that "Foxp3 regulatory T cells are known to suppress protective host immune responses to a wide variety of solid tumours, but their therapeutic targeting is largely restricted to their transient depletion or "secondary" modulation... Genetic or pharmacologic targeting of Usp7 impairs Foxp3 Treg suppressive functions, while conventional T cell responses remain intact. As a result, pharmacologic inhibitors of Usp7 can limit tumour growth in immunocompetent mice, and promote the efficacy of antitumour vaccines and immune checkpoint therapy with anti-PD1 monoclonal antibody in murine models. Hence, pharmacologic therapy with Usp7 inhibitors may have an important role in future cancer immunotherapy"

Dr. Hancock notes "Immunotherapy must do more than affect a single target, since those approaches help only about 20% of patients. Pharmacologic inhibition of USP7 allows direct targeting through the immune system, in a graded manner that has antitumor efficacy used alone or combined with one or more biologic agents.”

“We are pleased that Progenra’s USP7 inhibitors, tested in several laboratories worldwide, can eradicate cancers by both tumoricidal and immunological mechanisms,” added Tauseef Butt, President of Progenra. “We are excited to move USP7 inhibitors into clinical trial as single agents or combined with marketed immunological agents.”

Source: EBioMedicine