Table 1.
Adenoviral vectors
| Virus name | Mechanism | In vitro | In vivo | Delivery route | Reference |
|---|---|---|---|---|---|
| Retargeted | |||||
| FGF2-Ad-TK | FGF2 receptor targeting by a conjugate of FGF2 linked to a Fab’ fragment against the adenoviral knob region | N/A | ⇓ Tumor MVD and antitumor effects in HNSCC xenografts | IT | 40 |
| MHESpcAdluc | Polymer-coated Ad linked to monoclonal antibodies against human E-selectin | Infects umbilical cord ex vivo | N/A | N/A | 41 |
| PSGL-1-Fc-StrepGpcAdluc (in vivo) | Polymer-coated Ad linked to PSGL-1 | N/A | Co-localizes with CD31+ cells in HCC xenografts | IV | |
| Ad-uPAR-MMP-9 | Replication-deficient Ad expressing uPAR and MMP-9 antisense transcripts | ⇓ Cancer cell-induced EC capillary formation | ⇓ Tumor growth and lung metastasis in NSCLC xenografts | IT, IV | 50 |
| KOX/PEGbPHF | pH-sensitive oncolytic adenovirus expressing a VEGF transcriptional repressor | ⇓ VEGF expression ⇓ Vessel sprouting |
⇓ MVD and antitumor effects in rat glioma | IV | 43 |
| Ad5/35LacZ | CD 46 dependent endothelial binding | Efficient infection of endothelial cells | Rat HCC model: Colocalization of viral β-gal with CD46, CD31, Flk1 | Via hepatic artery | 42 |
| VB-111 | Ad-5 containing a pre- proendothelin 1 promoter (PPE-1-3X) and Fas-chimera transgene | N/A | Transgene expression and apoptosis in tumor-associated ECs | IV | 37 |
| Ad5ROBO4 | Replication-competent Ad5 containing ROBO4 promoter | N/A | RCC model: Tumor EC infection ⇓ MVD |
IV | 38 |
| Armed | |||||
| Ad5H2E-PPE1(3x)-ASMase | Endothelial targeted expression of acid sphingomyelinase | Specificity toward ECs | Melanoma; fibrosarcoma: Tumor EC-specific targeting ⇑ EC apoptosis |
IV | 112 |
| Ad-ΔB7-shVEGF | VEGF-specific shRNA expressing Ad vector | ⇓ Tube formation ⇓ Vessel sprouting (rat aortic ring assay) |
Matrigel plug assay ⇓ Vascularization ⇓ Tumor growth in multiple tumor models |
IT | 44 |
| Ad-ΔE1-U6shIL8 | Replication-competent Ad expressing IL-8 shRNA | ⇓ Migration and tube formation ⇓ Vessel sprouting (rat aortic ring assay) |
Breast cancer lung metastasis model; ⇓ VEGF and IL-8 ⇓ Tumor MVD |
IT | 113 |
| CRAd-S-5/3shMMP14 | Fiber-modified Ad vector expressing MMP14 shRNA | N/A | Glioma xenografts ⇓ CD31+ cells |
IC | 114 |
| Ad5/3-9HIF-Δ24-VEGFR-1-Ig | Hypoxia targeted Ad vector expressing soluble VEGF receptor 1-Ig fusion protein | Minimal HUVEC cytotoxicity | RCC xenografts: ⇓ Tumor size ⇓ Tumor MVD |
IT | 45 |
| Ad5/F35-XAF1 | Expression of tumor suppressor gene XAF1 | ⇓ VEGF mRNA and protein expression | HCC xenografts: ⇓ Tumor VEGF expression ⇓ Tumor MVD |
IT | 115 |
| ZD55-IL-18 | E1B gene deleted Ad expressing IL-18 | N/A | Melanoma xenografts: ⇓ VEGF ⇓ CD34 positive cells |
IT | 116 |
| EndoAngio-PRRA | Prostate-restricted Ad5 expressing Endostatin–angiostatin fusion protein | Conditioned media ⇓ EC proliferation, migration, and tube formation |
Prostate cancer xenografts: antitumor effects ⇓ Tumor MVD |
IT | 53 |
| pAd-2S03 | Ad expressing a scAb intrabody that inhibits mouse and human Tie-2 surface expression | Effective intrabody expression in ER of ECs | Human Kaposi’s sarcoma and colon carcinoma ⇓ Tumor MVD |
Peritumorally | 117 |
| Ad-eTie1-GALV | Ad encoding GALV fusogenic membrane glycoprotein regulated by human endothelial receptor tyrosine kinase (eTie1) | Heterocellular syncytia between tumor-associated endothelial cells and tumor cells | HEK 293 xenografts: heterocellular syncytia between infected ECs and HEK 293 cells lead to virus replication in vivo | IV | 118 |
| Combination | |||||
| Ad Flk1-Fc + Dl922/947 | Soluble VEGFR2 expressing Ad vector Oncolytic Ad virus selective for G1–S cell cycle checkpoint loss |
N/A | Prostate and colon cancer xenografts: ⇑ Antitumor effects ⇓ Tumor MVD |
IT IV |
47 |
| Ad-Endo + Ad-H101 | Replication-deficient Ad encoding human endostatin + replication-competent Ad | ⇓ ECs proliferation | NPC xenografts: combined treatment ⇑ Endostatin expression ⇑ Antitumor effects |
IT | 51 |
| dl922-947 + bevacizumab | E1 gene deleted Ad + anti-VEGF monoclonal antibody | N/A | Thyroid carcinoma; ⇑ Tumor viral distribution ⇓ MVD |
IT | 119 |
| AdVIL-24 + ionizing radiation | Ad5E1- and E3-deleted adenovirus expressing human IL-24 and GFP | N/A | NPC xenograft models: ⇓ Tumor MVD ⇓ VEGF expression ⇑ Antitumor effects |
IT | 59 |
Abbreviations: Ad, adenovirus; β-gal, β-galactosidase; EC, endothelial cell; ER, endoplasmic reticulum; FGF, fibroblast growth factor; GALV, gibbon ape leukemia virus; HEK, human embryonic kidney cells; HCC, hepatocellular carcinoma; HNSCC, head and neck squamous cell carcinoma; IC, intracranial; IL, interleukin; IT, intratumoral; IV, intravenous; MMP-9, matrix metallopeptidase 9; MVD, microvessel density; N/A, not applicable; NPC, nasopharyngeal carcinoma; NSCLC, non-small-cell lung cancer; PPE-1-3X, pre-proendothelin promoter; PSGL, P-selectin glycoprotein ligand-1-Fc fusion; RCC, renal cell cancer; ROBO4, roundabout4; scAb, single chain antibody; shRNA, short hairpin RNA; uPAR, urokinase receptor; HUVEC, human umbilical vein endothelial cell; VEGF, vascular endothelial growth factor; VEGFR, VEGF receptor; ⇑, increased; ⇓, decreased.