USP7 Program

USP7: a DUB with strong oncology links and is an established anti-cancer target.

Lead optimization program

Therapeutic Rationale

USP7 is implicated in controlling the suppressive capacity of regulatory T cells (Tregs) in vivo through regulating FOXP3 (van Loosdregt et al., 2013), meaning that USP7 inhibition may potentiate immune-mediated killing of cancer cells.

USP7 stabilizes regulatory T cell (Treg) specific transcription factor FOXP3 by blocking its proteasomal degradation. Consequently, inhibiting USP7 reduces FOXP3 expression, impairs suppressive capacity and induction of new Tregs, thereby enhancing anti-tumour responses.

Inhibition of Tregs is therefore an attractive therapeutic approach for cancer. Mission has identified potent and selective USP7 inhibitors with Treg inhibitory activity in vitro and tumor growth inhibition activity in vivo.

Given the recent success of immune-modulatory anti-cancer therapies in clinical trials, Mission aims to validate this aspect of USP7 biology with its small-molecule inhibitors.

Aspects of this research are supported by Innovate UK funding of £1.9 million.