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. 2017 Mar 21;5:20–40. doi: 10.1016/j.omto.2017.03.002

Table 1.

OVs Encoding p53 or p53 Family Members

OV Name Virus Genome Modifications Transgene Location in Viral Genome Transgene Modifications Cancer Targeted Toxicological Study In Vitro Effects In Vivo Tumor and Mice Models Virus Dose (Total) and Injection Mode In Vivo Effects Therapeutic Combination References
Adenovirus SG600-p53 E1a CR2-deleted 24 nt (nt 923–946); E1a under hTERT promoter; E1b under HRE cis-elements TP53 between E1a and E1b WT gene under CMV promoter yes 1–4 × 1011 VP/kg (i.v.) for safety pharmacology, 2.5 × 1013 VP/kg (i.m.) for acute toxicity test via one injection ↑ safety ↑ toleration no adverse effects 57
Adenovirus SG600-p53 E1a CR2-deleted 24 nt (nt 923–946); E1a under hTERT promoter; E1b under HRE cis-elements TP53 between E1a and E1b WT gene under CMV promoter lung, liver, cervical, pancreas no ↑ oncoselectivity ↑ p53 expression ↑ cytotoxicity lung subcutaneous xenograft (NCI-H1299) BALB/c nude mice 5 × 108 to 2 × 109 PFU (i.t.) via five injections ↓ tumor growth ↑ necrosis areas ↑ p53 level in cancer cells injected ↑ apoptosis 168
Adenovirus SG635-p53 E1a CR2-deleted 24 nt (nt 923–946); E1a under hTERT promoter; E1b under HRE cis-elements Ad35 (shaft + knob) TP53 between E1a and E1b WT gene under CMV promoter breast no ↑ infectivity ↑ viral replication ↑ p53 expression ↑ viral progeny production ↑ cytotoxicity breast subcutaneous xenograft (Bcap-37) BALB/c nude mice 1 × 109 PFU (i.t.) via five injections ↑ cell growth inhibition ↑ necrosis area ↑ viral progeny production ↑ p53 level in cancer cells injected 169
Adenovirus AdSurp-p53 E1a under Survivin promoter TP53 upstream E1a WT gene under CMV promoter gallbladder, hepatic no ↑ cytotoxicity ↑ oncoselectivity ↑ p53 level ↑ viral proliferation gallbladder subcutaneous xenograft (EH-GB1) BALB/c nude mice 1 × 109 PFU (i.t.) via five injections ↑ tumor growth inhibition ↑ p53 expression in cancer cells ↑ apoptosis ↑ necrosis area 170
Adenovirus AdCB016-mp53(268N) E1a CR1-deleted (aa 27–80); E1a CR2-deleted 24 nt (aa 122–129) TP53 in E3 mutation (D268N) cervical no ↑ oncoselectivity ↑ cytotoxicity ↑ resistance to HPV E6 ↑ p53 transactivation function in E6-positive cells ND ND ND 94
Adenovirus OV.shHDAC1.p73 E1a CR2-deleted 24 nt (nt 923–946); shHDAC1 between E4 and right terminal repeat TP73 in fiber WT gene melanoma no ↑ cytotoxicity lifting of epigenetic blockage ↑ apoptosis ↑ autophagy no inhibition of viral replication ↑ viral progeny production subcutaneous xenograft (SK-Mel-147) NMRI nude mice 3 × 108 PFU (i.t.) via three injections ↓ tumor growth no recurrence ↑ survival shRNA against HDAC1 127
Adenovirus Adp53rc ADP deletion TP53 in fiber; E3 deletion WT gene lung no no inhibition of viral replication ↑ viral spread ↑ p53 level exogenous p53 in the nucleus ↑ oncolytic activity ↑ apoptosis 171
Adenovirus Adp53W23S ADP deletion; E3 deletion TP53 in fiber mutation (W23S) lung, colorectal no no inhibition of viral replication ↑ viral spread ↑ resistance to E1b-55kD and MDM2 nuclear localization of p53 no export to cytosol ↑ p53 level ↑ p53 half-life (stability) ↑ cytotoxicity mildly decreased p53 transactivation subcutaneous xenograft (A549) NCrNU-M nude mice 1 × 109 PFU (i.t.) via one injection Tumor size unaffected by p53 expression ↑ p53 expression in cancer cells from virus-infected areas p53 nuclear expression 83
Adenovirus AdΔ24-p53 E1a CR2-deleted 24 nt (aa 122–129) TP53 in E3 WT gene diverse human cancer cells no ↑ cytotoxicity ↑ early virus release oncolysis independent of E1a binding to pRb and independent of E3 functions 74
Adenovirus AdΔ24-p53 E1a CR2-deleted 24 nt (aa 122–129) TP53 in E3 WT gene neuroblastoma no ↑ cytotoxicity effect independent of endogenous p53 cellular status subcutaneous xenografts (IGR-N91, IGR-NB8) SPF-Swiss athymic nude mice 5 × 108 PFU (i.t.) via five injections ↓ tumor growth ↑ cell lysis ↑ apoptosis ↑ fibrous fascicles ↑ necrosis areas 76
Adenovirus AdΔ24-p53 E1a CR2-deleted 24 nt (aa 122–129) TP53 in E3 WT gene glioma, glioblastoma no ↑ cytotoxicity effect independent of endogenous p53 cellular status replication in normal brain tissue ex vivo, but low amount of progeny virus produced subcutaneous xenografts (IGRG88, IGRG121) SPF-Swiss athymic nude mice 5 × 107 to 5 × 109 PFU (i.t.) via five injections ↓ tumor growth ↑ mice survival no inhibition of viral replication ↑ apoptosis ↑ inflammatory cell infiltration (lymphocyte, macrophage) ↑ necrosis areas 75
Adenovirus AdΔ24-p53 E1a CR2-deleted 24 nt (aa 122–129) TP53 in E3 WT gene glioma no ↑ cytotoxicity with radiotherapy no change of viral replication with radiotherapy ↑ apoptosis with radiotherapy, radiotherapy does not increase p53 phosphorylation no increase of p53 on co-treatment outcome subcutaneous xenograft (U-87MG) SPF-athymic nude mice 1 × 109 PFU (i.t.) via three injections ↓ tumor growth viral replication allowed no detection of exogenous p53 ↑ survival no benefits brought by exogenous p53 radiotherapy 106
Adenovirus AdΔ24-p53(14/19) E1a CR2-deleted 24 nt (aa 122–129) TP53 in E3 mutation (2 nt substitutions) T > A leading to L14Q; T > G leading to F19S gastric, osteosarcoma, lung, ovarian, astrocytoma no ↑ cytotoxicity ↑ resistance to MDM2 ↑ p53 stability ↑ p53 half-life mutation provokes moderate loss of p53 transactivation function 172
Adenovirus S7605-11R-p53 E1a under hTERT promoter; absence of E1b and its promoter too TP53 in E3 fused with 11R (polyarginine peptide), CMV promoter gallbladder no ↑ cytotoxicity ↑ oncoselectivity BALB/c nude mice (EH-GB2) 1 × 109 PFU (i.t.) via five injections ↓ cell growth ↑ necrotic foci ↑ p53 level in cells ↑ apoptosis 99
VSV-mp53 WT murine TP53 between G and L WT gene breast, melanoma yes WT M protein blocks host mRNA export ↑ oncoselectivity ↑ p53 level TS/A-luc tumor cells (injected i.v.) in BALB/c mice and BALB/c nude mice 5 × 107 or 5 × 108 PFU (i.v.) via one injection for toxicity test, increasing doses from 1 × 108 to 1 × 109 PFU (i.v. and i.n.) ↑ virus attenuation in immunocompetent mice ↓ cell growth ↑ mice survival fatal toxicity after i.n. injection in nude mice 62
VSV-M(mut)-mp53 M (matrix protein) mutations (aa 52–54) murine TP53 between G and L WT gene breast, melanoma yes M(mut) allows host mRNA export ↑ oncoselectivity ↑ p53 level TS/A-luc tumor cells (injected i.v.) in BALB/c mice and BALB/c nude mice 5 × 107 or 5 × 108 PFU (i.v.) via one injection for toxicity test, increasing doses from 1 × 108 to 1 × 109 PFU (i.v. and i.n.) ↑ virus attenuation in immunocompetent mice ↓ toxicity ↓ cell growth ↑ mice survival ↑ anti-tumor immunity (IFN, CD49b+ NK, CD8+ T responses) ↓ inflammatory cytokines (IL-6, IP-10) fatal toxicity after i.n. injection in nude mice 62
VSV-p53wt M (matrix protein) mutation ΔM51 TP53 between G and L WT gene pancreas no no inhibition of viral replication ↑ oncoselectivity ↓ IFN response (NF-κB inhibition) nuclear localization of exogenous p53 67
VSV-p53CC M (matrix protein) mutation ΔM51 TP53 between G and L chimeric p53CC pancreas no no inhibition of viral replication ↑ oncoselectivity ↓ IFN response (NF-κB inhibition) counteract dominant-negative effects from endogenous mutant p53 nuclear localization of exogenous p53 67
Newcastle disease virus rNDV-p53 WT TP53 between F and HN WT gene hepatoma yes ↓ cell growth ↑ exogenous p53 level no inhibition of viral replication with exogenous p53 ↑ early apoptosis (reduction of mitochondrial membrane potential) subcutaneous xenograft (H22) ICR mice 1 × 107 PFU (i.t.) via one injection 10 systemic injections for toxicity study ↓ tumor growth ↑ mice survival ↑ apoptosis no toxicity and no serum chemistries changes 61

Mode of injections: i.m., intramuscular; i.n., intranasally; i.t., intratumoral; i.v., intravenous. CMV, cytomegalovirus; CPU, colony-forming unit; ND, not determined; PFU, plaque-forming unit; VP, viral particles.