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Review
. 2021 Feb 3;13(4):588.
doi: 10.3390/cancers13040588.

Oncolytic Virotherapy in Solid Tumors: The Challenges and Achievements

Affiliations
Review

Oncolytic Virotherapy in Solid Tumors: The Challenges and Achievements

Ke-Tao Jin et al. Cancers (Basel). .

Abstract

Oncolytic virotherapy (OVT) is a promising approach in cancer immunotherapy. Oncolytic viruses (OVs) could be applied in cancer immunotherapy without in-depth knowledge of tumor antigens. The capability of genetic modification makes OVs exciting therapeutic tools with a high potential for manipulation. Improving efficacy, employing immunostimulatory elements, changing the immunosuppressive tumor microenvironment (TME) to inflammatory TME, optimizing their delivery system, and increasing the safety are the main areas of OVs manipulations. Recently, the reciprocal interaction of OVs and TME has become a hot topic for investigators to enhance the efficacy of OVT with less off-target adverse events. Current investigations suggest that the main application of OVT is to provoke the antitumor immune response in the TME, which synergize the effects of other immunotherapies such as immune-checkpoint blockers and adoptive cell therapy. In this review, we focused on the effects of OVs on the TME and antitumor immune responses. Furthermore, OVT challenges, including its moderate efficiency, safety concerns, and delivery strategies, along with recent achievements to overcome challenges, are thoroughly discussed.

Keywords: antitumor immune response; delivery; genetic modification; oncolytic virus; tumor microenvironment.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Recent approaches in oncolytic virotherapy. Expression of TAA-receptors and scFvs, recombination of specific domains and motifs, using tumor-specific promoters, and application of miRNA-TS could enhance the tumor targeting. GMOVs expressed inflammatory cytokines, enzymes, chemokine receptors, costimulatory molecules, and proapoptotic proteins achieve high antitumor potency. ECM and vasculature degradation by enzymes and molecules result in a higher spread of OVs. Administration routs are a critical factor in achieving better results with lower adverse effects. Besides, deleting virulence genes and recombination of OVs together could diminish the concerns of adverse events. However, several biosafety concerns still remained unmet. The combination of OVT with other immunotherapy, such as ICIs, TIL therapy, CART cell therapy, DC vaccines, mAbs, BiTEs, and metabolic inhibitors could potentiate the immunotherapy against tumors. OV. Oncolytic virus; OVT. OV therapy; TAA. Tumor-associated antigen; scFv. Single-chain variable fragment; Her-2. Human epidermal growth factor receptor 2; EpCAM. Epithelial cell adhesion molecule; CEA. Carcinoembryonic antigen; AdV. Adenovirus; RGD. Arginine-glycine-aspartate; GP-160. Glycoprotein-160; miRNA-TS. microRNA targeting sequence; PSA. Prostate-specific antigen; hTERT. Human telomerase reverse transcriptase; DC. Dendritic cell; CD. Cytosine deaminase; 5-FC. 5-fuorocytosine; 5-FU. 5-fluorouracil; HPGD. Hydroxyprostaglandin dehydrogenase; PGE2. Prostagalndin-E2; MDSC. Myeloid-derived suppressor cell; IFN. Interferon; TRAIL. TNF-related apoptosis-inducing ligand; siRNA. Small interfering RNA; TLR-9. Toll-like receptor-9; ICI. Immune checkpoint inhibitor; BiTE. Bispecific T cell engager; mAb. Monoclonal antibody; TIL. Tumor0infiltraring lymphocyte; CART cell. Chimeric-antigen receptor T cell; TME. Tumor microenvironment; ECM. Extracellular matrix; VEGF. Vascular-endothelial growth factor.

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