Review Article

Oncolytic Virus-Based Immunotherapies for Hepatocellular Carcinoma

Table 2

Representative OVs used in preclinical studies.

Virus strainModificationTherapeutic geneHCC cell lines usedAnimal modelDose (pfu)
and route
Reference

Adenovirus, CV890AFP transcriptional regulatory
elements (TRE) to control an
artificial E1A-IRES-E1B bicistronic
cassette in an ad5 vector
None, combination
with doxorubicin
HepG2, Huh7,
Hep3B, and SNU449
BALB/c nude mice
Hep3B/HepG2 xenografts
1 × 1011 IV[74]
Adenovirus,
ZD55-TRAIL/ZD55-
Smac
Deletion of E1B 55KDa gene
Insertion of
EGFP, TRAIL/Smac genes
TRAIL/SmacHep3B, BEL7404,
and SMMC7721
BALB/c nude mice
BEL7404 xenograft
2 × 109 IT[67]
Adenovirus, CNHK500Human telomerase reverse
transcriptase (hTERT) and
hypoxia-response promoter
controlled the E1b gene
hTERTHep3B, HepGII, and
SMMC-7721
BALB/c nude mice,
SMMC-7721, and
Hep3B xenografts
2 × 108–2 × 109 IT[68]
Adenovirus, CNHK300hTERT was inserted with viral genome at upstream of E1A regionhTERTHepGII and Hep3BNo animal model usedMOI of
5 pfu/cell
[69]
Adenovirus,
ZD55-IFN-β
E1B-55-kDa gene deletions and hIFN-β insertionhIFN-βHep-G2 and BEL7404BALB/c nude mice,
BEL7404 xenografts
2 × 109 IT[70]
Adenovirus, SG7011let7TInsertion of eight
copies of
let-7 target sites (let7T) into
the 39 untranslated region
of E1A
miRNA, let-7HepG2, Hep3B,
PLC/PRF/5, and Huh7
BALB/c nude mice,
Hep3B and SMMC-7721
xenografts
5 × 108 IT[71]
Adenovirus, TelomelysinhTERT inserted upstream
of the E1 gene
hTERTHuman: Huh-7,
Hep3B, PLC5, HA22T,
HCC36, and HepG2
Mouse: Hepa-1c1c7
and Hepa 1–6
HBx transgenic mice,
orthotopic model
Low: 1.25 × 108
Medium: 6.25 × 108
High: 3.0 × 109 IT
[72]
Adenovirus,
Ad-ΔB/TRAIL and Ad-ΔB/IL-12
Mutated in E1A and deleted in E1B regions. Insertion
of hTRAIL or hIL-12
hTRAIL or hIL-12Hep3B and HuH7Athymic nude mice,
orthotopic model
2 × 108
1 × 1010 IV
[73]
HSV, designated
liver-cancer specific
oncolytic virus (LCSOV)
Viral glycoprotein H gene linked with
liver-specific
apolipoprotein
E (apoE)-AAT
promoter. miR-122a complimentary
sequence to the 3′ untranslated
region (3′UTR). miR-124a and
let-7 also inserted at 3′ UTR
miR122miR-124a
and let-7
HuH-7, HepG2,
and Hep3B
Hsd: athymic (nu/nu) mice,
Hep3B xenograft
5 × 106 IT[75]
HSV, G47ΔICP47 and
γ34.5-deletion
NoneHepG2, HepB, SMMC-7721, BEL-7404, and BEL-7405Balb/c nude mice SMMC-7721,
BEL-7404 xenograft
2 × 107 IT[76]
MeV, (Res + MeV)Encoding of GFP as a marker
gene and SCD as suicide gene
None
Combination with HDACi drug resminostat (Res)
HepG2 and Hep3BNo animal model usedVarious MOIs[89]
NDVL289A mutation within the
F gene
NoneHepG2 and Huh7Buffalo rats
McA-RH7777 rat
HCC-orthotopic model
108 TCID50/rat HAI[90]
VV, JX-594Deletion of TK and VGF,
insertion of h GM-CSF
hGM-CSFNoneImmunocompetent,
orthotopic, NZW rabbits. VX2 tumor model. Rat: chemically induced HCC
Rabbit:
1 × 108–1 × 109 IV/IT
Rat: 1 × 108 IT
[79]
VV, JX-963Deletion of TK and VGF,
insertion of h GM-CSF
hGM-CSFNoneImmunocompetent,
orthotopic, NZW rabbits
VX2 tumor model
Various IV[80]
VV, GLV-1 h68Deletion of TK and insertion
of Renilla luciferasegreen
fluorescent protein (Ruc-GFP),
β-galactosidase, β-glucuronidase
NoneHuH7 and
PLC/PRF/5
Athymic Nude-Foxn1nu
HuH7 and PLC xenografts
5 × 106 IV[82]
VV, GLV-1 h68Deletion of TK and insertion of Renilla luciferasegreen
fluorescent protein (Ruc-GFP),
β-galactosidase, β-glucuronidase
NoneHuh-7, Hep 3B,
SNU-449 and SNU-739
No animal model usedMOI of 0.001, 0.01, 0.1, and 1[83]
VV, GLV-2b-372Deletion of TK and insertion
of TurboFP635 gene
NoneHuh-7, Hep G2,
SNU-449, and SNU-739
Athymic nude mice
Huh-7 xenograft
1 × 105 IT[84]
VSV, rVSV-GFPInsertion of GFPNoneHuman: Hep 3B and Hep G2
Rat: McA-RH7777
Buffalo rats
McA-RH7777 orthotopic, syngeneic
1 × 108 IT[85]
VSV, rVSV-β-galInsertion of
β-galactosidase (β-gal)
NoneMcA-RH7777Buffalo rats
McA-RH7777 orthotopic
1.3 × 107 HAI[86]
VSV, rVSV-NDV/F(L289A)Insertion of NDV/FNoneHuman: Hep 3B and
Hep G2
Rat: McA-RH7777
Buffalo rats, orthotopic syngeneic McA-RH77771.3 × 107 HAI[8587]
VSV, rVSV-NDV/F(L289A)Insertion of NDV/FNoneHuman: Hep 3B and
Hep G2
Rat: McA-RH7777
Buffalo rats, orthotopic syngeneic McA-RH77771.3 × 107 HAI[88]
VSV, rVSV(MΔ51)-M3MΔ51deletion and M3 additionNoneMcA-RH7777Buffalo rats
McA-RH7777 orthotopic
5.0 × 107–5.0 × 109 HAI[69]

IV: intravenous; IT: intratumoral; MOI: multiplicity of infection.