Inhibiting TBK1 to overcome resistance to immunotherapy

Inhibiting TBK1, a serine/threonine kinase that integrates signals from cytosolic nucleic acid sensors to regulate interferon responses, could help treat solid tumors by increasing cytotoxic responses to effector cytokines, overcoming resistance to immunotherapy.

In patient-derived organotypic tumor spheroid models of solid tumors including immunotherapy-resistant metastatic cutaneous melanoma, a benzonitrile-based small molecule TBK1 inhibitor plus an anti-PD-1 mAb decreased tumor cell viability compared with either agent alone. ...