The METIOR Incubator: Checkpoints Team

Project Description

Advances in immunotherapy have revolutionized the means by which clinicians treat human cancer. Immunotherapies referred to as ‘checkpoint’ inhibitors unleash ‘restrained’ components of a patient’s existing immune defenses against cancerous cells. While certain tumors exhibit dramatic responses to checkpoint inhibitors, ovarian tumors are largely refractory to checkpoint inhibitors for reasons that remain poorly understood. A surprising potential link tumor immunogenicity and efficacy of checkpoint inhibition may be the epigenetic regulation of endogenous retroviruses. Endogenous retroviruses form double-stranded RNAs (dsRNAs) that stimulate antiviral responses against cancer cells. In preclinical models of ovarian cancer, therapeutic activation of endogenous retroviruses slightly improves the efficacy of immune checkpoint blockade. This project seeks to expand upon these observations to identify biomarkers associated with active dsRNA responses in ovarian tumors, and to identify therapeutics or biologics that may further enhance dsRNA response to augment immune checkpoint blockade in ovarian cancer.

Team Roster

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Arnab Ghosh, MD, PhD
Memorial Sloan-Kettering Cancer Center

Charles Ishak, PhD
Princess Margaret Cancer Centre

Jacob Shabason, MD
Pearlman School of Medicine, University of Pennsylvania

Grey Wilkinson, PhD
Oncolytics Biotech Inc.

John Yi, PhD
Duke University Medical Center