Table 2.
Adenoviral vectors for cancer treatment in clinical trials.
| OncAd | Modification | Transgene | Disease | Administration | Phase | Clinical Trial NO. | Clinical Trial State | Combination | Main Results of Completed Studies |
|---|---|---|---|---|---|---|---|---|---|
| Ad5-yCD/mutTKSR39rep-ADP | E1B55K-deleted (the 34183bp to 35673bp encoding 55 kDa protein in E1B region is deleted) |
yCD/TK | Prostate Cancer | IPR | 2 | NCT00583492 | Completed | Radiation | No serious virus-related side effects; meaningful reduction in positive biopsy results for 2 years [11] |
| Ad5-yCD/mutTKSR39rep-hIL12 | E1B55K-deleted (Same as above) |
yCD/TK, hIL-12 | Metastatic pancreatic cancer | IV | 1 | NCT03281382 | Recruiting | n/a | |
| Ad.hIFN-beta | E1/partial- deleted, E3-deleted | IFN-α2b | Mesothelioma | IPL | 1 | NCT01119664 | Completed | Pemetrexed /Cisplatin | No serious toxicities; no biologic parameters found correlating with reponses to the treatment; median overall survival time of 12.5 months [12] |
| AdVince | CgA-E1A (CHGA gene (CgA promoter)-driven E1A expression) | miR122 target sequences, PTD | Neuroendocrine tumors | IH | 1, 2 | NCT02749331 | Recruiting | n/a | |
| CG0070 | E2F-E1A (E2F-1 promoter-drivenE1A expression) | GM-CSF | Bladder Cancer | IVE | 2 | NCT02365818 | Completed | No serious adverse effects; an overall 47% (21/45) CR rate at 6 months for all patients and 50% for patients with CIS [13] | |
| Colo-Ad1 | Ad11p/Ad3 (Ad11p backbone with a large deletion in the E3-region, a small E4-domain (E4orf4) deleted, and a partial E2B substitution by the Ad3 E2B) |
Colon, NSCLC, Bladder, Renal Cancer | IT, IV | 1 | NCT02053220 | Completed | No treatment-associated serious adverse events; specific virus delivery in most tumor samples, high local CD8+ cell infiltration in 80% (8/10) of tumor samples [14] | ||
| CRAd-S-pk7 | Survivin promoter-driven E1A expression | pk7 (polylysine) | Brain Cancer | NSC, IC | 1 | NCT03072134 | Completed | Radiation, chemotherapy | Not reported |
| DNX-2401 | E1A Δ24, RGD (a 24 bp deletion (bp 923-946; the Rb-binding domain) in the E1A gene and the insertion of an RGD integrin-binding motif (4C peptide: Cys-Asp-Cys-Arg-Gly-Asp-Cys-Phe-Cys) in the H1 loop of the Ad fiber) | Glioblastoma; gliosarcoma tumor | IT | 2 | NCT02798406 | Active, not recruiting | Pembrolizumab | n/a | |
| Brain cancer | BM-hMSCs, IA | 1 | NCT03896568 | Recruiting | n/a | ||||
| Brainstem glioma | IT | 1 | NCT03178032 | Completed | Not reported | ||||
| Glioblastoma, Gliosarcoma | IT | 1 | NCT02197169 | Completed | IFNγ | No serious virus-related adverse effects; poor tolerability of IFNγ; IFNγ did not provide additional benefit; 50% of patients with a baseline tumor diameter of ≤ 42 mm survived beyond 12 months | |||
| Brain cancer | IT, CI | 1 | NCT00805376 | Completed | No serious toxicities; active virus replication in tumor; median overall survival time of 9.5 months for single IT; median overall survival time of 13.0 months for permanently implanted catheter [15] | ||||
| Glioblastoma Multiforme | IT, IM | 1 | NCT01956734 | Completed | Temozolomide | No severe virus-related toxicities; FGF2 as a prognostic biomarker of DNX-2401 treatment response [16] | |||
| ICOVIR-5 | E2F-E1A Δ24, RGD (E2F-1 promoter-drivenE1A Δ24 expression, the insertion of an RGD integrin-binding motif (4C peptide) in adenoviral fiber) | Melanoma | IV | 1 | NCT01864759 | Completed | Not reported | ||
| Solid tumors | MSC, IV | 1, 2 | NCT01844661 | Completed | No serious toxicity; adenovirus replication in 78% (7/9) patients; circulating CD8+T cells raised [17] | ||||
| LOAd703 | 5/35, E1A-Δ24 (Substituting the fiber domain of Ad5 with the corresponding domain of Ad35, E1A-24 bp in Ad5 is deleted) |
TMZ-CD40L and 4-1BBL | Malignant melanoma | IT | 1, 2 | NCT04123470 | Recruiting | Atezolizumab | n/a |
| Pancreatic cancer | IT | 1, 2 | NCT02705196 | Recruiting | Atezolizumab, nab-paclitaxel | n/a | |||
| Pancreatic, Ovarian, Biliary, Colorectal cancer | IT | 1, 2 | NCT03225989 | Recruiting | Gemcitabine/Cisplatin, Gemcitabine/Oxaliplatin | n/a | |||
| OBP-301 | hTERT promoter (hTERT promoter-driven E1A expression) |
Hepatocellular carcinoma | IT | 1 | NCT02293850 | Recruiting | Radiation | n/a | |
| Advanced solid tumor | IT | 1 | NCT03172819 | Recruiting | Pembrolizumab | n/a | |||
| Esophageal cancer | IT | 1 | NCT03213054 | Recruiting | n/a | ||||
| Esophagogastric adenocarcinoma | IT | 2 | NCT03921021 | Recruiting | n/a | ||||
| ONCOS-102 | Ad5/Ad3, E1A-Δ24 (Substituting the knob domain of Ad5 with the corresponding domain of Ad3, E1A-24 bp in Ad5 is deleted ) | GM-CSF | Melanoma | IT | 1 | NCT03003676 | Active, not recruiting | Cyclophosphamide, Pembrolizumab | n/a |
| Prostate cancer | IT | 1, 2 | NCT03514836 | Recruiting | DCVAC/PCa, Cyclophosphamide | n/a | |||
| Peritoneal malignancies | IP | 1, 2 | NCT02963831 | Recruiting | Durvalumab | n/a | |||
| Solid tumour | IV, IT | 1 | NCT01598129 | Completed | Cyclophosphamide | No dose limiting toxicity or maximum tolerated dose was identified; 40% (4/10) evaluable patients had disease control based on PET/CT scan at 3 months; a prominent infiltration of TILs to tumors was seen post-treatment in 92% (11 /12) patients; median overall survival was 9.3 months [18] | |||
| VCN-01 | DM-1-E2F-E1A Δ24, RGD (insulate the E2F1 promoter using DM-1 insulators, E2F-E1A Δ24 and RGD as ICOVIR-5) |
Hyaluronidase | Head and neck neoplasms | IV | 1 | NCT03799744 | Recruiting | Durvalumab | n/a |
| Pancreatic adenocarcinoma | IT | 1 | NCT02045589 | Completed | Gemcitabine and Abraxane® | Not reported |
Note 1: Clinical trial data are from ClinicalTrials.gov: Home [19]; Note 2: oncolytic adenoviruses (OAs) listed in alphabetical order in this table are Ad5-based vectors. If modifications were introduced into the vector, these are indicated in the “Modification” column; Note 3: Abbreviation: BM-hMSCs, bone-marrow-derived human mesenchymal stem cells delivery. CgA, chromogranin A. CI, cancer surrounding brain tissue injection. CIS, carcinoma-in-situ. CR, complete remission. DCVAC/PCa, dendritic cells (DCs) pulsed with killed LNCaP prostate cancer cells. EV, endovenous injection. FGF2, fibroblast growth factor 2. GM-CSF, granulocyte-macrophage colony-stimulating factor. hTERT, human telomerase reverse transcriptase. IA, intra-arterial injection. IC, intracerebral injection. IFNγ, interferon gamma. IH, intrahepatic artery infusion. IM, intramural injection. IP, intraperitonealy infusion. IPL, intrapleural infusion. IPR, intraprostatic infusion. IT, intratumoral injection. IV, intravenous injection. IVE, intravesical intervention. MSC, mesenchymal stem cell delivery. n/a, not applicable because results of this trial are not available. NSC, neural stem cell. NSCLC, non-small cell lung cancer. PTD, protein transduction domain. RGD, Arg-Gly-Asp amino acid sequence as target of αv integrins. TK, herpes simplex virus 1 thymidine kinase. TMZ, trimerized membrane-bound isoleucine zipper. yCD, yeast cytosine deaminase.