Proteomic analysis of plasma exosomes as biomarkers of response to MVP-S based immunotherapy

Abstract

Abstract Ovarian cancer is a deadly gynaecological disease owing to its late-stage diagnosis. Recurrence and chemo-resistance develop despite initial treatment success. Maveropepimut-S (MVP-S), formerly DPX-Survivac, is a DPX-based immune educating therapy that elicits robust, targeted and, sustained specific anti-tumor T- and B-cell responses in advanced ovarian cancer patients. Exosomes are a subtype of extracellular vesicles (EVs) secreted by cells involved in intercellular communication. They contain bioactive molecules that can influence the tumor, the immune system, and the extracellular environment. Hence, circulating exosomes could provide real time assessment of disease evolution making them ideal minimally invasive biomarkers for monitoring response to immunotherapies. Plasma exosomes were isolated from advanced ovarian cancer patients (n=22) at pre- and on-treatment with MVP-S based therapy (DeCidE1 trial, NCT02785250). Subjects with clinical benefit (>10% tumor shrinkage) to therapy displayed a lower overall total EV protein concentration. Untargeted proteomic profiling by liquid chromatography tandem mass spectrometry identified 227 proteins in exosomes. Of these, 95 (42%) were likely from non-tumor exosomes and involved in immune modulation such as regulation of humoral response and B-cell immunity. When compared to the plasma proteome, 128 (56%) proteins were found to be exclusive to exosomes. Functional annotations of these proteins suggest their role in modulating immune pathways related to Fc receptor mediated signaling and T-cell migration. The results highlight the potential value of plasma exosome assays for monitoring disease and as a potential surrogate response biomarker. Supported by -IMV inc. -NRC-IRAP R&D Certificate Program.