Engineering Oncolytic Adenoviruses with VSVG‐Decorated Tumor Cell Membranes for Synergistically Enhanced Antitumor Therapy. (7th November 2022)

• Record Type: Journal Article
• Authors: Huang, Li‐Li; Wang, Weiwei; Wang, Zhongjie; Zhang, Han; Liu, Houli; Wu, Guanghao; Nie, Weidong; Xie, Hai‐Yan
• Is Part Of: Advanced functional materials. Volume 33:Number 3(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-11-07
• Subjects: immunotherapy -- low‐pH activated membrane fusions -- oncolytic adenoviruses -- tumor cell membranes -- vesicular stomatitis virus glycoprotein; Materials -- Periodicals; Chemical vapor deposition -- Periodicals; 620.11
• DOI: 10.1002/adfm.202209056
• Languages: English
• ISSNs: 1616-301X

Abstract

Abstract: Oncolytic viruses hold great promise for cancer treatment but their practical applications are seriously impaired by a series of limitations. Herein, an engineered oncolytic adenovirus (OA) is constructed that can boost both the direct oncolysis and antitumor immune response of OA attributed to the increased tumor targeting and low‐pH responsive fusogenic activity. The tumor cell membranes are decorated with vesicular stomatitis virus glycoprotein (VSVG) via vesicular stomatitis virus (VSV) infection and then used to mask OA (V‐M@OA). After systemic administration, the engineered OA can target homologous tumors owing to the homing ability of tumor membranes. Then the unique low‐pH responsive fusogenic activity of VSVG significantly enhances the replication of OA by promoting the whole virus infection process, resulting in remarkable virus‐mediated tumoricidal effects and thus abundant in situ released tumor‐associated antigens (TAAs). Meanwhile, VSVG on V‐M@OA augments the adjuvanticity of OA and thus significantly enhancing the antitumor immune response. The synergism of virus‐mediated killing and immune effects leads to significant tumor inhibition with no obvious side effects. Abstract : An engineered oncolytic adenovirus (OA) is constructed by coating OA with vesicular stomatitis virus glycoprotein‐decorated tumor cell membranes. The obtained V‐M@OA can overcome the series of limitations of OA‐based tumor therapy, enhancing both the direct oncolysis and antitumor immunology. It provides a novel idea to put forward the universal application of OA in oncolytic virotherapies.