|
Virus
|
Viral gene defect
|
Anticancer cDNA
|
Prodrug> Metabolite
|
Effect
|
Reference
|
|
HSV1A: hrR3, MGH1,
G207 (Medigene, Inc.)
|
ICP6 and/or
ICP34.5
|
TK
|
Ganciclovir>GCV-Phosphate
|
Predominant
anticancer action in some situations, but increased antiviral
action in others (figure 5)
|
(42-49) .
|
|
HSV1: rRp450
|
ICP6
|
CYP2B1
|
Cyclophosphamide>
Phosphoramide Mustard
|
Predominant
anticancer action + immunosuppressive effects.
|
(15)
|
|
Adenovirus: FGR
|
E1B55kD
|
Fused TK-CD gene
|
Ganciclovir> GCV-Phosphate
+ 5-fluorocytosine> 5fluorouracil
|
Combination
of FGR, GCV, 5FC and radiation shows predominant anticancer
action
|
(50)
|
|
HSV1: Fu-10
|
Unknown
|
Fusogenic glycoprotein
|
Not applicable
|
Enhanced fusion of cell membranes caused by replicating
virus increases anticancer effect
|
(51)
|
|
Adenovirus: ad5/IFN
|
E3
|
Interferon
|
Not applicable
|
Increased
anticancer effect compared to control E3-deleted adenovirus
|
(52)
|
|
Adenovirus; Ad.TKRC,Ad.OW34
|
E1B55KD
|
TK
|
Ganciclovir> GCV-Phosphate
|
Contradictory
anticancer effects
|
(53, 54)
|
|
Adenovirus:
Ig.Ad5E1+.E3TK
|
E3-19K
|
TK
|
Ganciclovir> GCV-Phosphate
|
Increased
anticancer effect in glioma
|
(55)
|
|
HSV1: Mix of G207 + Defective
HSv-IL2B
|
ICP6 and ICP34.5
|
IL2
|
Not applicable
|
At
low dose, the mix was more effective than either virus alone
|
(56)
|
|
HSV1: NV1042
|
Complexc
|
IL12
|
Not applicable
|
Increased
anticancer effect
|
(57)
|
|
HSV1: Mix of G207 + Defective
HSV-soluble B7-1B
|
ICP6 and ICP34.5
|
Soluble B7-1
|
Not applicable
|
Increased
anticancer effect
|
(58)
|
|
HSV1: HSV1yCD
|
ICP6
|
Yeast cytosine deaminase
|
5-fluorocytosine>
5-fluorouracil
|
Increased
anticancer effect minimal antiviral effect
|
(59)
|
|
Vaccinia: VCD
|
TK
|
Bacterial cytosine deaminase
|
5-fluorocytosine>
5-fluorouracil
|
Increased
effect at low viral dose
|
(60)
|
|
HSV1
|
ICP34.5
|
IL4, IL12, IL10
|
Not applicable
|
Increased
anticancer effect for IL12 and IL4, but antagonistic effect
for IL10
|
(61, 62)
|
A See Table 3 for detailed description
B Represents a 1:1 mix of OV g207 and replication-defective HSV expressing cytokine
cDNA. Based on the “Piggyback” concept, first shown in ref.
(63)
C An intertypic HSV1/HSV2 recombinant derived from R7020 (NV1020 – Medigene, Inc.)
resulting in deletion of: Ul55, UL56, one copy of ICP0,
ORF 0 and ORF P and reinsertion of: TK with ICP4 promoter;
HSV2 glycoprotein G,D,I,E (64)
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