Grant: Master's Award: Canada Graduate Research Scholarships - Master's program

Ovarian cancer (OC) remains one of the most lethal gynecologic malignancies worldwide. Traditional OC treatments often induce systemic toxicity and chemoresistance, highlighting the need for novel strategies. Immunogenic cell death (ICD) offers a promising approach by remodeling the tumour microenvironment (TME) to stimulate antitumour immunity and immunological memory through the release of danger-associated molecular patterns (DAMPs). Synthetic double-stranded RNA (dsRNA) such as poly(I:C) can act as an effective immune stimulant and potential ICD-inducer. The phytoglycogen nanoparticle, Nanodendrix (NDX), functions as a dsRNA carrier that offers protection from degradation as well as enhanced dsRNA immune activation and OC cell death. This study aims to determine whether poly(I:C)-NDX induces ICD in OC cells and to evaluate its ability to bridge innate antiviral and adaptive antitumour immunity. Key DAMPs indicative of ICD including calreticulin (CRT) exposure, extracellular adenosine-triphosphate (ATP) secretion, and high mobility group box-1 (HMGB1) release, will be quantified. Adaptive immune stimulation will be determined by assessing cell signalling molecules including type I interferon and major histocompatibility complex I, that would translate to adaptive immune stimulation within the body. This research aims to advance the current understanding of ICD-inducing agents and their potential as effective immunotherapeutic strategies with applications beyond oncology. Moreover, identifying poly(I:C)-NDX as an ICD-inducer capable of bridging innate and adaptive immune responses could reveal a novel, immune-supportive strategy that reduces treatment-related toxicity, improving long-term tumour control and OC patient quality of life.