BioCentury
ARTICLE | Distillery Therapeutics

Pretreatment with STAT1 activators, IL-10 blocker to improve response to checkpoint inhibitors

August 22, 2019 9:31 PM UTC

INDICATION: Melanoma; mesothelioma; renal cancer

Activating STAT1 and blocking IL-10 prior to checkpoint inhibitor administration could improve efficacy in patients with mesothelioma, melanoma and other cancers. High intratumoral expression of a gene signature associated with STAT1 signaling -- which IFNγ and TLR3 induce -- as well as low intratumoral IL-10 levels prior to treatment was associated with increased response to Tecentriq atezolizumab in urothelial cancer patients and Opdivo nivolumab in melanoma patients. In mice bearing mesothelioma, melanoma or kidney cancer-derived tumors, pretreatment with a cocktail containing IFNγ, a TLR3 agonist and a mAb against IL-10 prior to treatment with anti-CTLA-4 plus anti-PD-L1 mAbs increased survival from 0-10% to 20-80%. The triple combination provided no benefit when administered after the checkpoint inhibitors. Next steps include testing the pretreatment cocktail in combination with checkpoint inhibitors in clinical trials...