Immunotherapy combining tumor and endothelium cell lysis with immune enforcement by recombinant MIP-3α Newcastle disease virus in a vessel-targeting liposome enhances antitumor immunity

• DOI: 10.1136/jitc-2021-003950
• Publication Date: 2022-03-07T15:46:36Z
• Authors: Jin-Yan Wang; Hengyu Chen; Shu-Zhen Dai; Feng-Ying Huang; Ying-Ying Lin; Cai-Chun Wang; Lei Li; Wu-Ping Zheng; Guang-Hong Tan
• Keywords: Virotherapy

Background Several agents for oncolytic immunotherapy have been approved clinical use, but monotherapy is modest most agents. The combination of several therapeutic strategies through recombinant and nanotechnology to engineer multifunctional viruses a promising strategy. Methods An endothelium-targeting iRGD-liposome encapsulating Newcastle disease virus (NDV), which expresses the dendritic cell (DC) chemokine MIP-3α (iNDV3α-LP), three control liposomes were constructed. MIP-3α, HMGB1, IgG, ATP detected by western blotting or ELISA. chemotaxis DCs was examined Transwell chambers. phenotypes immune cells analyzed flow cytometry. antitumor efficiency investigated in B16 4T1 tumor-bearing mice. Immunofluorescence immunohistochemistry used observe localization liposomes, molecular expression angiogenesis. Synergistic index calculated using data tumor volume, angiogenesis tumor-infiltrating lymphocytes. Results Compared with NDV-LP, treatment iNDV3α-LP NDV3α-LP induced stronger replication lysis human umbilical vein endothelial (HUVECs) best response observed following treatment. treated produced more damage-associated pattern molecules, including secreted ATP, calreticulin. Moreover, specifically bound αvβ3-expressing HUVECs neovasculature. Tumor growth significantly suppressed, survival longer iNDV3α-LP-treated B16-bearing 4T1-bearing A mechanism study showed that initiated strongest tumor-specific cellular humoral response. could suppress reverse suppressive microenvironment both Conclusions In this study, had functions, such as vessel lysis, immunotherapy, binding its suppressed reversed immunosuppressive microenvironment. These findings offer strong rationale further investigation into strategy formulation study.