Abstract 4066: AnnexinV: Multifunctional anticancer immunotherapeutic protein in tumor microenvironment

Abstract

Abstract Introduction: After cancer treatment using chemotherapy and radiotherapy, tumor microenvironment continually occurs inflammation, which depend on damage-associated molecular pattern (DAMPs) released from apoptotic tumor cells. In this case, tumor microenvironment is regarded as inflammation zone and induce various immune cells infiltration, pro- and anti-inflammatory cytokines production and interaction between immune cells and cancer cells. These, a dynamic and complex microenvironment induce a favorable state for tumor growth. Thus, recent studies assert that it is important to regulate excessively increased inflammatory response in the tumor microenvironment accordingly. Annexin V is a Ca2+-dependent phospholipid binding pro[[Unsupported Character - Codename ­]]tein and known to bind to exposed phosphatidylserine on the apoptotic cells. Several groups and our study have recently demonstrated that annexin V has anti-inflammatory effects by inhibiting bone-marrow derived dendritic cell (BMDCs) activation and pro-inflammtory cytokine production. So, we suggest that Annexin V as a therapeutic approach for controlling inflammatory response in cancer patients having increased inflammation in tumor microenvironment. Methods: The size and purity of recombinant proteins were assessed using SDS-PAGE. IVIS imaging system used to characterize the accumulation of Annexin V containing protein into tumor loci in tumor-bearing mice. Therapeutic efficacy was confirmed tumor-specific CD8+ T cells in PBMCs and splenocytes by Flow cytometry analysis. pro-, anti- inflammtory cytokines and various immune cells infiltration in tumor microenvironment were examined by ELISA and FACS. Cytotoxicity by tumor-specific CD8+ T cells of Luciferase-expressing tumor cells was observed by representative luminescence imaging system. Results: The Targeting efficiency of Annexin V protein into tumor microenvironment was increased compared to control. Therapeutic efficacy was demostrated activation of tumor-specific CD8+ T cells (P < 0.001), inhibition of tumor growth (P < 0.05) and increase of survival (P < 0.05) in tumor bearing mouse compared to control. AnnexinV protein administration was decreased significantly TGF-beta 1 cytokine production (P < 0.001) and immunosuppressive cells infiltration (P < 0.001) in tumor microenviroment compared to non-treated group. Conclusion: We identified multiple role of Annexin V protein, which has capacity of apoptotic tumor cell target, as regulator of excessive inflammation in tumor microenvironment. This results could primarily pave the road for the development of anti-tumor immunotherapy. Citation Format: Jung Hwa Park, Young Seob Kim, Hyun Jin Park, Gun Young Jang, T.c. Wu, Yeong-Min Park, Tae Heung Kang. AnnexinV: Multifunctional anticancer immunotherapeutic protein in tumor microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4066.