Abstract TMIM-077: MYXOMA VIRUS ENHANCES TREATMENT BENEFIT OF CHEMOTHERAPY AND DENDRITIC CELL IMMUNOTHERAPY IN OVARIAN CANCER PRECLINICAL MODEL

Myxoma virus (MYXV) is a poxvirus with oncolytic and immunotherapeutic potential in many cancer models, including ovarian cancer (OC). Moreover, MYXV synergizes with chemotherapy including cisplatin for OC treatment. In this study, we used a p53-/- ID8 mouse model that closely portrays human high-grade serous OC to test MYXV virotherapy. We combined MYXV regime with cisplatin treatment and an innovative Th17-inducing dendritic cell (Th17-DC) vaccine currently being tested in clinical trials with OC patients. For DC immunotherapy, bone marrow-derived DC were pulsed with peptides from Sp17, a cancer testis antigen highly expressed in human OC and the ID8 mouse model. For MYXV virotherapy, we examined both wild-type and a replication-defective MYXV that is engineered without an essential viral immunomodulator called M062 (M062R-null MYXV). We found that inoculation with replication-competent MYXV improves survival when administered before cisplatin therapy. Interestingly, when the replication-defective M062R-null MYXV was used, improved survival was observed with virotherapy after the cisplatin treatment. We further found that M062R-null MYXV treatment provided long-lasting survival in combination with cisplatin and Th17-DC immunotherapy. Related studies showed that M062R-null MYXV infection in murine and primary human OC cells stimulated robust type I IFN expression and pro-inflammatory cytokines. Moreover, M062R-null MYXV activates type I IFN in macrophages and expression of inflammatory cytokines (e.g., CXCL-10 and IL-6). In conclusion, we propose that MYXV virotherapy provokes a type I interferon response and inflammatory cytokines that modulate the tumor microenvironment and enhance protective immune responses to Th17-DC vaccination for OC treatment. Citation Format: Steven J Conrad, Bernice Nounamo, Martin Cannon, Jia Liu. MYXOMA VIRUS ENHANCES TREATMENT BENEFIT OF CHEMOTHERAPY AND DENDRITIC CELL IMMUNOTHERAPY IN OVARIAN CANCER PRECLINICAL MODEL [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr TMIM-077.