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. Author manuscript; available in PMC: 2010 May 1.
Published in final edited form as: Curr Drug ther. 2009 May 1;4(2):117–138. doi: 10.2174/157488509788185123

Table 1.

Examples of Ad vectors for cancer gene therapy

Ad vector Tumor targeting
modification		 E3
status		 Effector
gene		 Basis of tumor
selectivity/antitumor
action		 Tumor type Route of
inoculation		 Combination
therapy		 Success
rate/response		 Clinical
phase		 Ref.
ONYX-015 E1B 55 kDa deletion ✘ None Defect in p53/late mRNA export Head and neck cancer i.t. None Objective response rate of 21% II [306]
ONYX-015 E1B 55 kDa deletion ✘ None Defect in p53/late mRNA export Head and neck cancer i.t. 5-FU + Cisplatin Objective response rate of 63% II [57]
ONYX-015 E1B 55 kDa deletion ✘ None Defect in p53/late mRNA export Solid tumor/advanced carcinoma i.v. Enbrel* 4/9 patients showed stable disease I [307]
H101 E1B 55 kDa deletion ✘ None Defect in p53/late mRNA export Head and neck or esophagus squamous cell cancer i.t. Cisplatin + 5- FU or adriamycin +5-FU Objective response rate of 72.7% with chemotherapy III [61]
CG5757

  • E1A under E2F-1 promoter

  • E1B under hTERT promoter

  • E1B-19 kDa deletion

 ✓ None

  • Upregulated E2F-1 and hTERT activity

  • TNF-α mediated selective replication

 Bladder transitional cell carcinoma, lung or prostate cancer xenograft mouse models i.t.or i.v. None Regression in tumor growth rate by ~72% PC [308]
CG7870

  • E1A under rat probasin promoter

  • E1B under PSA promoter

 ✓ None Upregulated probasin/PSA promoter activity LNCaP xenografts mouse model i.t. Radiation Drop in serum PSA Synergistic effect or radiation in tumor regression PC [287]
AdE4PSES E1a E1A and E4 under PSES bidirectional promoter ✓ None Upregulated PSA/PSMA activity CWR22rv prostate tumor cells in xenograft mouse model i.t. or i.v. None Tumor growth regression PC [114]
HILMI E1A and E1B under TCF response elements ✓ None Activated Wnt pathway Anaplastic thyroid cancer xenograft mouse model i.t. None Delay in tumor growth PC [309]
Ad5- CD/TKrep E1B 55 kDa deletion ✘ CD/HSV- TK

  • Defect in p53/late mRNA export

  • GDEPT

 Prostate cancer i.pr. Radiation therapy, 5-FC+ vGCV Significant decline in PSA levels in all patients I [143]
Ad5CMV- p53 (INGN201; Advexin) None (Replication incompetent) ✘ p53 Restoration of p53 function Esophageal squamous cell carcinoma i.t. None 6/10 patients had stable disease til l1yr I/II [20]
Ad-mda7 (INGN241) None (Replication incompetent) ✘ mda7/IL24 Mda7-mediated cytotoxicity Advanced cancer(multiple cancer types) i.t. None Tumor cell apoptosis, immuneactivation I [310]
E10A None (Replication ✘ Endostatin Anti-angiogenesis Solid tumors i.t. None Mild antitumor I [311]
OC- CAVE1(Canine Ad-2) E1A under osteocalcin promotor ✓ None Upregulated osteocalcin activity D22 canine osteosarcoma cells in xenograft mouse model i.t. None Tumor growth regression PC [286]
(Ad5Luc1- CK1) Ad5 containing CAV-1 knob ✓ None Enhanced transduction Cancer cell lines/ovarian cancer/liver primary tissue slices In vitro None Superior transduction than Ad5 PC [261]
Ad5.pk7-Δ24

  • E1A deletion

  • pK7 on Ad5 fiber

 ✓ None

  • Defect in Rb

  • Enhanced transduction

 Orthotopic breast cancer mouse model i.t. or i.v. None Regression in tumor growth PC [312]
Ad5/3- RGD Ad5 with Ad3 knob having RGD motif ✓ None Enhanced transduction Human glioma xenograft mouse model i.t. None 1000 fold increased infectivity than Ad5 PC [313]
Internavec

  • Deletion in E1A

  • E1A and E4 under human E2F1 promoter

 ✘ siRNA targeting k-ras

  • Defect in Rb

  • upregulated E2F1 activity

  • k-ras knockdown

  • Human cancer cells

  • Pancreatic cancer

  • xenograft mouse model

  • In vitro

  • i.t.

 None

  • 10 fold increased potency

  • Regression in tumor growth by 85.5%

 PC [158]
Ad.IFN-β None (Replication incompetent) ✘ IFN-β IFN-β mediated cytotoxicity and immune stimulation Malignant pleural mesothelioma and metastatic pleural effusions i.p. None 7/10 – antitumor immune response4/10 – Objective response I [314]
YKL- IL12/B7 E1B 55 kDa deletion ✘ IL-12 and B7–1

  • Defect in p53/late mRNA export

  • Immunostimulation

 Murine melanoma B16-F10 tumor model i.t. None Delayed tumor growth, increased survival rate, enhanced T-cell response PC [201]
TNFerade None (Replication incompetent) ✘ TNF-α under radio- induciblepromoter TNF- α mediated cytotoxicity and immunostimulation Soft tissue sarcoma i.t. Radiation therapy Objective response rate of 85% I [302]
Ad-E1A- COX E1A gene ligation to COX2 3′UTR ✘ None RAS/P-MAPK specific increased E1A mRNA stabilization

  • Cell culture

  • Xenograft mouse model

  • In vitro

  • i.t.

 None Increased oncolysis in tumor cells with high P-MAPK activity PC [136]
Ad5- CXCR4- UTR-E1A

  • Addition of 5′UTR from FGF-2 to E1A

  • E1A under CXCR4 promoter

 ✘ None

  • Increased E1A translation

  • Upregulated CXCR4 activity

  • Cell culture

  • Breast cancer xenograft mouse model

  • Human tissue slice model

  • In vitro

  • i.t.

 None Improvement in tumor selectivity PC [137]

✓, intact;

*

recombinant dimer of human TNF- α receptor;

✘

, partial or complete deletion; CAV, canine adenovirus; CD, cytosine deaminase; COX, cyclooxygenase; CXCR4, CXC chemokine receptor; E1A, E1B, E3, E4, Ad early genes; E2F, elongation factor; FGF, fibroblast growth factor; FU, fluorouracil; GCV, ganciclovir; HSV-TK, herpes simplex virus-thymidine kinase; hTERT, human telomerase reverse transcriptase; i.p., intrapleural; i.pr., intraproastatic; i.t., intratumoral; i.v., intravenous; IFN, interferon; IL, interleukin; MAPK, mitogen-activated protein kinase; MDA, melanoma-differentiation associated gene; PC, Pre-clinical; PSA, prostate-specific antigen; PSES, prostate-specific chimeric promoter-enhancer; PSMA, prostate-specific membrane antigen; Rb, retinoblastoma; siRNA, small interfering RNA; TCF, T-cell factor; TNF, tumor necrosis factor; UTR, untranslated region