Oncolytic virus therapy in cancer: A current review

Table 1 Genetic modifications in the adenovirus

Ref.	Virus	Updates	Aim
Rojas et al[219]	COVIR -7/-15	Insertion of E2F-binding sites in the gene E1A	Specific targeting to the tumor cells, which express E2F and increase viral replication rate and antitumor action
Sarkar et al[220]	CTV-m 7	Insertion of the transgene MDA-7/IL-24	Expression of the protein MDA-7/IL-24 increases the cytotoxic action in the tumor sites and lyse the metastatic cells. The studies have shown greater effectiveness in the therapy of prostate cancer
Sarkar et al[220]	tCCN1 -CTV - m 7	Replacement of E1A by tCCN1	Specific targeting and cytotoxicity against the tumor cells, which express the promoter tCCN1 in prostate cancer
Choi et al[221]	Ads armed with inhibitors of tumoral angiogenesis	Incorporation of the gene FP3	Increase of the antiangiogenic capacity, which decreases the vascular endothelial growth factor production and suppresses the rate of tumor growth
Lucas et al[222]	Ad5 armed with the peptide CKS17	Replacement of HVR5 by the peptide CKS17	Specific target to the TGFBRII in the liver cancer cells, increasing the viral cytotoxic action and decreasing the liver sequestration
Garofalo et al[223]	AdV-D24-ICOSL-CD40L	Insertion of D24, ICOSL and CD40 genes in the chimeric virus, AdV-D24, serotype 5/3	Selectivity to infect the cancer cells through DSG-2 receptor and stimulation of the immune system by ICOSL and ICOS, both contributing to the immunogenic cell death in melanoma
Vera et al[224]	VCN-01	Selectivity to the pRB pathway and ability to express hyaluronidase	Specific viral replication, decreasing the side effects and degradation of the extracellular matrix by the enzyme hyaluronidase in solid tumors
Yang et al[225]	Ad5/3-CXCR4-TIMP2	Replacing Ad5 knob with Ad3 knob and incorporating the gene TIMP2	Selective replication in the cancer cells, which reduces the action over the normal cells and the expression of inhibitors of metalloproteinases, contributing to the degradation and remodeling of the extracellular matrix, preventing tumor growth and metastasis

Ads: Adenoviruses; CD40L: CD40 ligand; DSG-2: Desmoglein 2; FP3: Farnesylated protein 3; HVR5: Hypervariable region 5; ICOSL: Inducible co-stimulator ligand; IL-24: Interleukin 24; MDA-7: Melanoma differentiation-associated gene-7; pRB: Retinoblastoma protein; tCCN1: Truncated cellular communication network factor 1; TGFBRII: Transforming growth factor-beta receptor II; TIMP2: Tissue inhibitor of metalloproteinases 2.

Table 2 Genetic modifications in the vaccinia virus

Ref.	Virus	Updates	Aim
Parato et al[226]	JX-594	Express GM-CSF and lacZ transgenes	Increase lytic activity and antitumor immunity
John et al[227]	vvDD-GFP	Insertion of an Ab specific for the costimulatory molecule 4-1BB	Increase antitumor responses with myeloid cells, greater infiltration of CD8+ effector T and NK cells
Zhang et al[228]	GLV-1 h68	Insertion of three expression cassettes into the A56R, F14.5L, and J2R	Increased tumor targeting specificity and reduced toxicity
Yoo et al[229]	CVV	Deletion of viral thymidine kinase genes	Regression of liver tumorigenicity and metastasis to the colon
Ricordel et al[230]	deVV5	TK-deleted chimeric VV armed with the suicide gene FCU1	Union of different VV strains, with increased oncolytic properties, with more efficient replication in human tumor cells
Ge et al[231]	vvDD-IL-12	Oncolytic VV delivering tethered IL-12	Increase tumor infiltration of activated CD4+ and CD8+ T cells, decrease the transforming growth factor β and increase interferon γ
Deng et al[232]	VG9	The oncolytic potency of VG9 was evaluated in various cell lines	Evaluate replication and cytotoxicity in vitro, antitumor effects and process of biodistribution of VG9 in a B16 tumor model

Ab: Agonist antibody; GM-CSF: Granulocyte-macrophage colony-stimulating factor; IL-12: Interleukin 12; NK: Natural killer; TK: Thymidine kinase; VV: Vaccinia virus.

Table 3 Genetic modifications in the herpes simplex virus-1

Ref.	Virus	Updates	Aim
Liu et al[61]	T-VEC	Insertion of GM-CSF and deletion of γ34.5, US12	Increase lytic activity and antitumor immunity
Ushijima et al[233]	HF10	Insertion of UL53, UL54 and deletionof UL43, UL49.5, UL55, UL56, LAT	Reduce neurovirulence and increase immunogenicity
Ebright et al[234]	NV1020	Incorporation of the HSV-1 TK gene and deletion of α0, α4, γ34.5, UL56, UL24	Reduce neurovirulence and provide susceptibility to antiviral chemotherapy
MacKie et al[235]	HSV 1716	Incorporation of γ34.5	Reduce neurovirulence
Mineta et al[236]	G207	Insertion of lacZ and deletion of γ34.5	Avoid ribonucleotide reductase encoding and reduce neurovirulence

GM-CSF: Granulocyte-macrophage colony-stimulating factor; HSV-1: Herpes simplex virus 1; LAT: Latency-associated transcript; T-VEC: Talimogene laherparepvec; TK: Thymidine kinase.