Engineering Oncolytic Adenoviruses with VSVG‐Decorated Tumor Cell Membranes for Synergistically Enhanced Antitumor Therapy

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.

Living virus‐based nanohybrids for biomedical applications

“…Strategies for optimizing the effectiveness of oncolytic viruses have been discussed in the above sections. Just a few more examples, Huang et al masked the oncolytic Ad with vesicular stomatitis virus glycoprotein (VSVG)-decorated tumor cell membranes (V-M@OA), effectively targeting the tumor and enhancing Ad infection due to the homologous targeting ability of tumor membranes and the unique low-pH responsive fusogenic activity of VSVG (Figure 4a; Huang, Wang, et al, 2022). The synergistic effect of oncolysis and immune activation led to significant tumor inhibition without obvious side effects.…”

“…(a) Schematic illustration of the preparation of V-M@OA and its application in synergistically enhanced antitumor therapy. Reprinted with permission from Huang, Wang, et al (2022) perforation or disruption (Xia et al, 2021). Under such circumstances, cell membranes pose a special barrier for non-enveloped viruses to penetrate.…”

“…(a) Schematic illustration of the preparation of V‐M@OA and its application in synergistically enhanced antitumor therapy. Reprinted with permission from Huang, Wang, et al (2022). (b) Technology road map of MRI‐guided focused ultrasound‐induced blood–brain barrier disruption to deliver BDNF retrovirus into the brain.…”

Co‐delivery of oncolytic virus and chemotherapeutic modality: Vincristine against prostate cancer treatment: A potent viro‐chemotherapeutic approach

“…9 The potency and pharmaceutical effectiveness of viral oncolytic activity depend upon the selection of tumor cells and more significant cytotoxicity at particular locations. 10 It leads to an immune-mediated effect against tumor cells by releasing different antigenic substances and specific tumors' inflammatory mediators. These factors eventually enhance patients' longevity.…”

“…Oncolytic viruses, including Edmonston‐derived strains of the OV vaccinia virus, parvovirus H1, and reovirus have demonstrated their efficacy for the treatment of different human carcinomas and are referred to as a triumph for the destruction of cancer cells in the modern era 9 . The potency and pharmaceutical effectiveness of viral oncolytic activity depend upon the selection of tumor cells and more significant cytotoxicity at particular locations 10 . It leads to an immune‐mediated effect against tumor cells by releasing different antigenic substances and specific tumors’ inflammatory mediators.…”