P08.46 Synergistic Therapeutic Efficacy via Immunomodulatory Platelet Rich Fibrin Patch (PRF-P) in Combination with Oncolytic Adenovirus for the Treatment of Glioma

Abstract

Abstract Introduction: Oncolytic virotherapy is an interesting approach for the treatment of cancer, including glioblastoma. Recent studies in this area suggest a synergistic approach to combine oncolytic virotherapy with immunomodulatory approaches. In this study, we have examined the role of platelet-rich fibrin patch (PRF-P) to enhance anti-tumoral immune response in immune-competent murine model C57/BL when used in conjunction with tumor specific oncolytic Ad5RGD-CMV-E1Δ24. This PRF-P is derived from blood, enriched with lymphocytes, platelets, macrophages (M1), and pro-inflammatory cytokines. Application of PRF-P has been shown to enhance immune cell migration and proliferation. HYPOTHESIS: We hypothesize that PRF-P provides local immunomodulation by supplying pro-inflammatory chemokines, as well as recruiting and enhancing proliferation of cytotoxic T cells, which may lead to an enhanced anti-tumoral immune response when combined with oncolytic virotherapy. METHODS: Blood from donor mice bearing GL261-OVA, a murine glioma cell line expressing ovalbumin (OVA), as a model antigen was collected into non-anticoagulant tubes and processed according to platelet-rich fibrin protocol. Five days after tumor implantation, a stereotactic intra-tumor injection of Ad5RGD-CMVΔ24 viral vector was performed. 48 hours post viral vector administration, a craniotomy was performed and the autologous PRF-P was applied over the tumor. For immunological flow and immunohistochemical analyses, mice were sacrificed five days post treatment. Results: We first performed a survival analysis in immuno-competent murine model. Mice injected with oncolytic virus alone had a significantly prolonged survival compared to PBS treated group (P<0.001). In addition, when used in combination with immunomodulatory PRF-P, this prolonged survival benefit was extended (P<0.001). Also, immunohistochemical analysis showed a decreased implanted tumor size in both virus alone and combinatory ­treatment groups. Most interestingly, we observed an increased number of tumor specific CD8+ cells and antigen cross-presenting and lymph node tropic dendritic cells (CD11b-/CD11C+/ CD103+) from therapeutic treatment groups. CONCLUSION: Our observation collectively represents a novel anti-glioma oncotherapy and immunomodulatory approach and provides a platform for the evaluation and translation of this promising anti-glioma strategy. We will further discuss additional immunomodulatory application: oncolytic virus expressing checkpoint inhibitor PD-1 along with the PRF-P treatment.