Table 1A. Summary of DNA, double-strand virus design, mechanisms of action and clinical implications.
| Virus | Design | Clinical Implications |
|---|---|---|
| Herpes Simplex Virus (HSV) | · T-VEC: ICP34.5/ICP47 mutant and US11/GM-CSF expressing [31] | · Melanoma [32, 33]. |
| · G207: ICP34.5/RR mutant [43, 61–63] | · Glioma [68, 69]. | |
| · NV1020: ICP34.5 mutant [70, 71]. | · CRC [72, 73]. | |
| · HFA10: RR mutant [75] | · Data for breast, head and neck, and pancreas cancer [74–76] | |
| Vaccinia Virus | · vvDD: TK mutant strain. Viral protein VGF binding to EGFR in cell surface [185–187]. | · Phase I: ITu administration safe; abscopal effect [188]. |
| · JX-594: TK mutant / GM-CSF expressing strain [189]. | · HCC [84] · Other solid tumors including CRC [85, 86] |
|
| · GL-ONC1: TK mutant / HA expressing [190]. | · Malignant Effusions: Intrapleural injection safe; prolongs disease stability in malignant mesothelioma [191]. · Peritoneal Carcinomatosis: IP administration safe [192]. · Solid tumors: IV administration, 18% SD as best response (lasting >6 months) – IHC revealed delivery to the tumor [193, 194]. |
|
| Adenovirus | · ONYX-015: E1B55 mutant [90] | · Head and Neck [92]. |
| · Adenovirus chimeras · Ad5-D24: serogroup 5, E1A-/Rb-binding site negative; selectively kills cells with an abnormal p16/Rb pathway [195] · CRAd: Ad5-D24 plus serogroup 3 knob [196] · DNX-2401: Ad5-D24 plus RDG (integrin receptor) [197] · Ad5/3-D24-GMCSF and CGTG-102: CRAd and DNX-2401 plus GM-CSF respectively [197, 198]. · ColoAd1: tumor selective Adenovirus 11/3 · Ad5/3, hTERT and CD40 ligand expressing strain has improved antitumor immunity/activity [18]. |
· Phase I: CRAd by IP safe, 60% SD [196]. · Phase I: DNX-2401 by ITu administration in glioma safe, 12% CR rate, 11 months OS [199] · Phase I: DX-2401 or Ad5-D24-RDG-GMCSF ITu in solid tumors safe, 27% with SD [197]. · Phase I: CGTG-102 ITu in sarcoma safe, 75% with SD [198]. CGTG-102 ITu in solid tumors plus oral low-dose cyclophosphamide safe, 40% with controlled disease at 3 months [172]. · ColoAd1 has low level of pre-existing host immunity [200] and potentially higher potency than ONYX-015 [201]. It is tested in a mechanism of action Phase I study [202]. |
|
| · CG0070: E1A gene is under the control of E2F, GM-CSF expressing [94]. | · Urothelial carcinoma [96] | |
| · CV764 and CN706: E1A gene is under the regulation of PSA [203, 204]. | · Potential role in prostate cancer | |
| · OBP-301: hTERT promoter regulates the expression of E1 genes [205]. | · Preclinical activity in a CRC [206] |
CR: complete response, CRC: colorectal cancer, DNA: deoxyribonucleotide nucleic acid, EGFR: epidermal growth factor receptor, GM-CSF: granulocyte macrophage-colony stimulating factor, HA: hemagglutinin, HCC: hepatocellular carcinoma, hTERT: human telomerase, ICP: infectious cell protein, IHC: immunohistochemistry, IP: intraperitoneal, ITu: intratumoral, IV: intravenous, RR: ribonucleotide reductase, SD: stable disease, TK: thymidine kinase, US11: HSV RNA binding protein, VGF: viral growth factor.