THER-16. INTERACTION OF IMMUNE SYSTEM WITH ONCOLYTIC MEASLES VIRUS THERAPY IN AN MV-SENSITIVE IMMUNOCOMPETENT MURINE MODEL OF MEDULLOBLASTOMA

Abstract

Abstract INTRODUCTION: Oncolytic viruses selectively replicate in tumor cells, and may attract immune cells into the microenvironment to stimulate a systemic antitumor response. We have shown efficacy of oncolytic measles virus (MV) against medulloblastoma (MB) in preclinical models. To study the effect of immune system on MV therapy, we have developed the first immunocompetent MV-sensitive murine model of Group 3 MB (CSCG model) and showed that intratumoral MV treatment of tumor-bearing mice significantly prolonged survival. Herein, we study the interaction of MV therapy and tumor immune microenvironment in this model. METHODS: Naive and MV-preimmunized mice were injected with 200,000 CSCG tumor cells in caudate putamen and tumor-bearing mice were treated identically with intratumoral MV injections (n=5 per group). Tumor growth was monitored by bioluminescence imaging and RT-PCR was performed to assess infiltrating CD4+ and CD8+ T cells in MV-treated and untreated control tumors. RESULTS: RT-PCR of untreated tumors shows an average of 43.4 ±1.45-fold and 13.24 ±1.34-fold increase in infiltrating CD8+T cells and CD4+T cells, respectively, compared to normal brain (n=3). Tumors that responded to MV therapy, but recurred had a dramatic decrease in infiltrating CD8+T cells (2.66 ±0.8-fold higher than normal brain). No significant difference in survival was observed between MV-naive and MV-immunized mice (p= 0.773), indicating that anti-measles immunity does not affect MV efficacy, an important point given that almost all patients have been vaccinated with MV. Long-term survivors, both naïve and MV-immune, remained tumor-free for at least 150 days post treatment. These mice (n=3) were re-challenged with a 3-fold higher number of tumor cells than the original injection, but tumor failed to grow for at least 50 days post-injection. CONCLUSION: This finding strongly suggests MV treatment induces anti-tumor immunity. Ongoing studies are being performed to dissect this immune response and to explore the possibility of enhancing it.