Table 1.
Adenoviral-based therapies used in EOC preclinical trials.
| Approach | Ad vectors | Strategies | Models | References |
|---|---|---|---|---|
| Conditional replication | Onyx-015 (dl1520) |
E1B-55-kD deletion, 24 bp deletion in E1A |
Human xenografts immunodeficient mice ip + ip* |
[49, 50, 179–181] |
| Onyx-015 + CDDP | ||||
| dl922-947 | ||||
| dl922-947 + paclitaxel | ||||
| Enhancing infectivity | Ad5-RGD | Targeting to ανβ-integrins (fiber/fiber and pIX), targeting to heparan sulfate |
Human xenografts immunodeficient mice sc + it*/ip + ip* |
[72–74] |
| Ad5-pK7 | ||||
| Ad5-RGD-pK7 | ||||
| Ad5-RGD-Δ24 | ||||
| Ad5-Δ24DoubleRGD | ||||
| Ad5/3-Δ24 | Chimeric 5/3 fiber |
Human xenografts immunodeficient mice sc + it*/ip + ip* |
[84, 85, 182] | |
| Ad5/3-Δ24 + gemcitabine/epirubicin | ||||
| Restricting replication | Ad5-VEGF | Inclusion of a variety of tissue-specific promoters | Human xenografts immunodeficient mice sc + it*/ip + ip* | [89–94, 96–98, 101] |
| Ad5-hTERT + CDDP | Ex vivo primary ovarian tumor tissue | |||
| Ad5-Δ24-SPARC | ||||
| Ad5RGD-Cox-2-Δ24 | ||||
| Ad5RGD-Survivin + CDDP | ||||
| Ad5/3-VEGF | ||||
| Ad5/3-SLPI | ||||
| Ad5/3-CXCR4 | ||||
| Ad5/3-Mesothelin | ||||
| Ad5/3-Survivin | ||||
| Ad5/3-MDR1 | ||||
| Ad5/3-∆24-MDR1 | ||||
| Increasing potency | Ad5-CD133-Cre + Ad5-LoxP-tBid | Inclusion of inducers of cell apoptosis, suicide genes, genes targeting angiogenesis, enhancers of drug sensitivity |
Human xenografts immunodeficient mice sc + it*/ip + ip* |
[102, 105–107, 109–111, 114, 140, 183] |
| Ad5/3-CXCR4-TIMP2 | Ex vivo primary ovarian tumor tissue | |||
| Ad5-TK + GCV | ||||
| Ad5Δ24-TK + GCV | ||||
| Ad5Δ24 + GCV | ||||
| Ad5-TK-SSTR + GCV | ||||
| Ad5RGD-TK-SSTR + GCV | ||||
| Ad5/3-TK + GCV | ||||
| Ad5/3-Δ24-TK + GCV | ||||
| Ad5- MDR1-CD + 5FC | ||||
| Ad5-STAT3 + CDDP | ||||
| Ad5-MnSOD + CDDP | ||||
|
dl922-947 + TNF-α RNAi /antibodies |
Reduction of acute immune stimulation |
Human xenografts immunodeficient mice ip + ip* |
[116, 117] | |
| Ad5/3-IL24 | Inclusion of immunostimulatory molecules |
Human xenografts immunodeficient mice sc + it*/ip + ip* |
[61, 63, 121–123] | |
| Ad5/3-ING4 | Ex vivo primary ovarian tumor tissue | |||
| Ad5/3-IL24/ING4 | sc/ip immunocompetent Syrian hamster (pancreatic) | |||
| Ad5/3-E2F-Δ24 | ||||
| Ad5/3-E2F-Δ24-hTNFα-IRES-hIL2 | ||||
| Ad5Δ24-GMCSF | ||||
| ONCOS-102 (Ad5/3Δ24-GMCSF) | ||||
| Overcoming physical barriers and immunosuppression | Ad5-A20 | Triple detargeting + targeting to ανβ-integrins, use of other serotypes and chimeric vectors |
Human xenograft immunodeficient mice ip + ip* |
[42, 77, 135, 144] |
| Ad5/48-A20 |
Immunocompetent mice ip + ip* |
|||
| Ad5NULL-A20 | Ex vivo ascites | |||
|
Ad11 OvAd1 (ColoAd1/Ad11p) | ||||
| Ad-hEndo/PEG-PEI | Encapsulation with polymers and liposomes |
Human xenografts immunodeficient mice sc + it*/ip + ip* |
[148–152] | |
| Ad-IAI.3B/PEI-HA | ||||
| Ad/PEG-FGF2 | ||||
| Ad5/pHPMA-EGF | ||||
| Ad5/pHPMA-cetuximab | ||||
| AR2011/MenSCs | Use of cellular carriers |
Human xenografts immunodeficient mice sc + it*/ip + ip* |
[156, 157] | |
| CRAd-S-pk7/NSCs |
Immunocompetent mice ip + ip* |
|||
| CRAd-S-pk7/NSCs + CDDP | ||||
| Enadenotucirev- EpCAM BiTE | Increased Ad-mediated cytotoxicity, stimulation of a proinflammatory TME and activation of endogenous T cells | Ex vivo ascites | [170, 171, 174, 178] | |
| Enadenotucirev-FAP BiTE |
Human xenografts immunodeficient mice sc + it* |
|||
|
Ad5/35-hTERT-CCAU-SIRPa-IgG1 Ad5/35+ +α-PD-L1-γ1 |
Immunocompetent mice ip + ip* |
CDDP cisplatin, ip intraperitoneal, RGD arginine‐glycine‐aspartic acid, pK7 polylysine, sc subcutaneous, it intratumoral, VEGF vascular endothelial growth factor, hTERT human telomerase reverse transcriptase, SPARC secreted protein, acidic, rich in cysteine, SLP secretory leukocyte protease inhibitor, MDR1 multidrug resistance gene 1, tBid truncated Bid, TIMP2 tissue inhibitor of metalloproteinase 2, TK thymidine kinase, GCV ganciclovir, SSTR somatostatin receptor, CD cytosine deaminase, 5FC 5-fluorocytosine, STAT3 single transducer and activator of transcription-3, MnSO manganese superoxide dismutase, TNF-α tumor necrosis factor α, GMCSF granulocyte-macrophage colony stimulating factor, PEG polyethyleneglycol, PEI polyethylenimine, HA hyaluronic acid increased, FGF2 Fibroblast Growth Factor 2, pHPMA poly hydroxypropyl methacrylamide, EGF epidermal growth factor, MenSCs Menstrual blood mesenchymal stem cells, NSCs neural stem cells, EpCAM epithelial cell adhesion molecule, BiTE bispecific T‐cell engager, FAP fibroblast activation protein, SIRPα-Fc signal regulatory protein α. *Indicates how the model was stablished + the route of administration of the Ad vectors.