Role of RGD-containing ligands in targeting cellular integrins: Applications for ovarian cancer virotherapy (Review)

Gamble,Lena J.; Borovjagin,Anton V.; Matthews,Qiana L.

doi:10.3892/etm_00000037

Role of RGD-containing ligands in targeting cellular integrins: Applications for ovarian cancer virotherapy (Review)

Authors:
- Lena J. Gamble
- Anton V. Borovjagin
- Qiana L. Matthews
View Affiliations

Affiliations: Division of Human Gene Therapy, Departments of Medicine, Pathology, Surgery, Obstetrics and Gynecology, The Gene Therapy Center, University of Alabama at Birmingham, Birmingham, AL, USA
Published online on: March 1, 2010 https://doi.org/10.3892/etm_00000037
Pages: 233-240

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The purpose of this article was to review the current strategies of targeted therapy to integrins and define the best course of future research in ovarian cancer targeting. Cell surface integrin targeting has been used as a strategy for targeted therapy of several diseases with some success. The combination of virotherapy and integrin-targeting shows promise as a method for targeting ovarian cancer. More specifically, targeting of ovarian cancer with integrin-directed adenoviruses may lead to therapy with fewer toxicities and side effects. This article offers a review of the benefits of integrin-specific targeted therapy for several diseases and proposes a unique anti-ovarian cancer strategy involving the combination of the above with virotherapy as a potential anti-ovarian cancer treatment.

View Figures

View References

1.	Ruoslahti E: RGD and other recognition sequences for integrins. Annu Rev Cell Dev Biol. 12:697–715. 1996. View Article : Google Scholar : PubMed/NCBI
2.	Hynes RO: Cell adhesion: old and new questions. Trends Cell Biol. 9:M33–M37. 1999. View Article : Google Scholar : PubMed/NCBI
3.	Carmeliet P: Mechanisms of angiogenesis and arteriogenesis. Nat Med. 6:389–395. 2000. View Article : Google Scholar : PubMed/NCBI
4.	Friedlander M, Brooks PC, Shaffer RW, Kincaid CM, Varner JA and Cheresh DA: Definition of two angiogenic pathways by distinct alpha v integrins. Science. 270:1500–1502. 1995. View Article : Google Scholar : PubMed/NCBI
5.	Cheresh DA: Human endothelial cells synthesize and express an Arg-Gly-Asp-directed adhesion receptor involved in attachment to fibrinogen and von Willebrand factor. Proc Natl Acad Sci USA. 84:6471–6475. 1987. View Article : Google Scholar
6.	Horton MA: The alpha v beta 3 integrin ‘Vitronectin receptor’. Int J Biochem Cell Biol. 29:721–725. 1997.
7.	Van De Wiele C, Oltenfreiter R, De Winter O, Signore A, Slegers G and Dierckx RA: Tumour angiogenesis pathways: related clinical issues and implications for nuclear medicine imaging. Eur J Nucl Med Mol Imaging. 29:699–709. 2002.PubMed/NCBI
8.	Kumar CC: Integrin alpha v beta 3 as a therapeutic target for blocking tumor-induced angiogenesis. Curr Drug Targets. 4:123–131. 2003. View Article : Google Scholar : PubMed/NCBI
9.	Hynes RO: Integrins: a family of cell surface receptors. Cell. 48:549–554. 1987. View Article : Google Scholar : PubMed/NCBI
10.	Smith JW, Vestal DJ, Irwin SV, Burke TA and Cheresh DA: Purification and functional characterization of integrin alpha v beta 5. An adhesion receptor for vitronectin. J Biol Chem. 265:11008–11013. 1990.PubMed/NCBI
11.	Koster J: The integrin page: Alpha-v/beta-5 integrin [Webpage]. Available from: http://www.geocities.com/capecanaveral/9629/avb5.htmuri. 1997.
12.	Nemeth JA, Nakada MT, Trikha M, et al: Alpha-v integrins as therapeutic targets in oncology. Cancer Invest. 25:632–646. 2007. View Article : Google Scholar : PubMed/NCBI
13.	Juliano RL: Membrane receptors for extracellular matrix macro-molecules: relationship to cell adhesion and tumor metastasis. Biochim Biophys Acta. 907:261–278. 1987.PubMed/NCBI
14.	Albelda SM, Mette SA, Elder DE, Stewart R, Damjanovich L, Herlyn M and Buck CA: Integrin distribution in malignant melanoma: association of the beta 3 subunit with tumor progression. Cancer Res. 50:6757–6764. 1990.PubMed/NCBI
15.	Gladson CL and Cheresh DA: Glioblastoma expression of vitronectin and the alpha v beta 3 integrin. Adhesion mechanism for transformed glial cells. J Clin Invest. 88:1924–1932. 1991. View Article : Google Scholar : PubMed/NCBI
16.	Bello L, Francolini M, Marthyn P, et al: Alpha(v)beta3 and alpha(v)beta5 integrin expression in glioma periphery. Neurosurgery. 49:380–390. 2001.PubMed/NCBI
17.	Gehlsen KR, Davis GE and Sriramarao P: Integrin expression in human melanoma cells with differing invasive and metastatic properties. Clin Exp Metastasis. 10:111–120. 1992. View Article : Google Scholar : PubMed/NCBI
18.	Felding-Habermann B, Mueller BM, Romerdahl CA and Cheresh DA: Involvement of integrin alpha v gene expression in human melanoma tumorigenicity. J Clin Invest. 89:2018–2022. 1992. View Article : Google Scholar : PubMed/NCBI
19.	Nip J, Shibata H, Loskutoff DJ, Cheresh DA and Brodt P: Human melanoma cells derived from lymphatic metastases use integrin alpha v beta 3 to adhere to lymph node vitronectin. J Clin Invest. 90:1406–1413. 1992. View Article : Google Scholar : PubMed/NCBI
20.	Gasparini G, Brooks PC, Biganzoli E, et al: Vascular integrin alpha(v)beta3: a new prognostic indicator in breast cancer. Clin Cancer Res. 4:2625–2634. 1998.PubMed/NCBI
21.	Landen CN, Kim TJ, Lin YG, et al: Tumor-selective response to antibody-mediated targeting of alphavbeta3 integrin in ovarian cancer. Neoplasia. 10:1259–1267. 2008.PubMed/NCBI
22.	Pap T, Gay R and Gay S: Mechanisms of joint destruction. Rheumatoid Arthritis. New Frontiers in Pathogenesis and Treatment. Firestein GS, Panayi GS and Wollheim FA: Oxford University Press; Oxford: pp. 189–199. 2000
23.	Koch AE: The role of angiogenesis in rheumatoid arthritis: recent developments. Ann Rheum Dis. 59(Suppl 1): i65–i71. 2000. View Article : Google Scholar : PubMed/NCBI
24.	Takayama K, Ueno H, Pei XH, Nakanishi Y, Yatsunami J and Hara N: The levels of integrin alpha v beta 5 may predict the susceptibility to adenovirus-mediated gene transfer in human lung cancer cells. Gene Ther. 5:361–368. 1998. View Article : Google Scholar : PubMed/NCBI
25.	Scotton CJ, Krupiczojc MA, Konigshoff M, et al: Increased local expression of coagulation factor x contributes to the fibrotic response in human and murine lung injury. J Clin Invest. 119:2550–2563. 2009.PubMed/NCBI
26.	Luna J, Tobe T, Mousa SA, Reilly TM and Campochiaro PA: Antagonists of integrin alpha v beta 3 inhibit retinal neovascularization in a murine model. Lab Invest. 75:563–573. 1996.PubMed/NCBI
27.	Kerr JS, Mousa SA and Slee AM: Alpha(v)beta(3) integrin in angiogenesis and restenosis. Drug News Perspect. 14:143–150. 2001.PubMed/NCBI
28.	Klotz O, Park JK, Pleyer U, Hartmann C and Baatz H: Inhibition of corneal neovascularization by alpha(v)-integrin antagonists in the rat. Graefes Arch Clin Exp Ophthalmol. 238:88–93. 2000. View Article : Google Scholar : PubMed/NCBI
29.	Hemminki A, Belousova N, Zinn KR, et al: An adenovirus with enhanced infectivity mediates molecular chemotherapy of ovarian cancer cells and allows imaging of gene expression. Mol Ther. 4:223–231. 2001. View Article : Google Scholar
30.	Arap W, Pasqualini R and Ruoslahti E: Cancer treatment by targeted drug delivery to tumor vasculature in a mouse model. Science. 279:377–380. 1998. View Article : Google Scholar : PubMed/NCBI
31.	Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T and Thun MJ: Cancer statistics, 2008. CA Cancer J Clin. 58:71–96. 2008. View Article : Google Scholar
32.	Choi M, Fuller CD, Thomas CR Jr and Wang SJ: Conditional survival in ovarian cancer: results from the SEER dataset 1988–2001. Gynecol Oncol. 109:203–209. 2008.PubMed/NCBI
33.	Bast RC Jr, Hennessy B and Mills GB: The biology of ovarian cancer: new opportunities for translation. Nat Rev Cancer. 9:415–428. 2009. View Article : Google Scholar : PubMed/NCBI
34.	Armstrong DK, Bundy B, Wenzel L, et al: Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med. 354:34–43. 2006. View Article : Google Scholar : PubMed/NCBI
35.	Schmidmaier R and Baumann P: Anti-adhesion evolves to a promising therapeutic concept in oncology. Curr Med Chem. 15:978–990. 2008. View Article : Google Scholar : PubMed/NCBI
36.	Chames P and Baty D: Antibody engineering and its applications in tumor targeting and intracellular immunization. FEMS Microbiol Lett. 189:1–8. 2000. View Article : Google Scholar : PubMed/NCBI
37.	Hudson PJ: Recombinant antibody constructs in cancer therapy. Curr Opin Immunol. 11:548–557. 1999. View Article : Google Scholar : PubMed/NCBI
38.	DeNardo SJ, Kroger LA and DeNardo GL: A new era for radio-labeled antibodies in cancer? Curr Opin Immunol. 11:563–569. 1999. View Article : Google Scholar : PubMed/NCBI
39.	Pasqualini R and Ruoslahti E: Organ targeting in vivo using phage display peptide libraries. Nature. 380:364–366. 1996. View Article : Google Scholar : PubMed/NCBI
40.	Hong FD and Clayman GL: Isolation of a peptide for targeted drug delivery into human head and neck solid tumors. Cancer Res. 60:6551–6556. 2000.PubMed/NCBI
41.	Wickham TJ, Roelvink PW, Brough DE and Kovesdi I: Adenovirus targeted to heparan-containing receptors increases its gene delivery efficiency to multiple cell types. Nat Biotechnol. 14:1570–1573. 1996. View Article : Google Scholar : PubMed/NCBI
42.	Dmitriev I, Krasnykh V, Miller CR, et al: An adenovirus vector with genetically modified fibers demonstrates expanded tropism via utilization of a coxsackievirus and adenovirus receptor-independent cell entry mechanism. J Virol. 72:9706–9713. 1998.
43.	Schottelius AJ, Zugel U, Docke WD, et al: The role of mitogen-activated protein kinase-activated protein kinase 2 in the p38/TNF-alpha pathway of systemic and cutaneous inflammation. J Invest Dermatol. Aug 6–2009.(Epub ahead of print).
44.	Schmieder AH, Caruthers SD, Zhang H, Williams TA, Robertson JD, Wickline SA and Lanza GM: Three-dimensional MR mapping of angiogenesis with alpha5beta1(alpha nu beta3)-targeted theranostic nanoparticles in the MDA-MB-435 xenograft mouse model. FASEB J. 22:4179–4189. 2008. View Article : Google Scholar : PubMed/NCBI
45.	Leroy-Dudal J, Demeilliers C, Gallet O, et al: Transmigration of human ovarian adenocarcinoma cells through endothelial extracellular matrix involves alphav integrins and the participation of MMP2. Int J Cancer. 114:531–543. 2005. View Article : Google Scholar
46.	Markland FS, Shieh K, Zhou Q, Golubkov V, Sherwin RP, Richters V and Sposto R: A novel snake venom disintegrin that inhibits human ovarian cancer dissemination and angiogenesis in an orthotopic nude mouse model. Haemostasis. 31:183–191. 2001.PubMed/NCBI
47.	Carreiras F, Thiebot B, Leroy-Dudal J, Maubant S, Breton MF and Darbeida H: Involvement of alphavbeta 3 integrin and disruption of endothelial fibronectin network during the adhesion of the human ovarian adenocarcinoma cell line IGROV1 on the human umbilical vein cell extracellular matrix. Int J Cancer. 99:800–808. 2002. View Article : Google Scholar
48.	Maubant S, Cruet-Hennequart S, Poulain L, et al: Altered adhesion properties and alphav integrin expression in a cisplatin-resistant human ovarian carcinoma cell line. Int J Cancer. 97:186–194. 2002. View Article : Google Scholar : PubMed/NCBI
49.	Hapke S, Kessler H, Luber B, et al: Ovarian cancer cell proliferation and motility is induced by engagement of integrin alpha(v) beta3/vitronectin interaction. Biol Chem. 384:1073–1083. 2003. View Article : Google Scholar : PubMed/NCBI
50.	Gutheil JC, Campbell TN, Pierce PR, Watkins JD, Huse WD, Bodkin DJ and Cheresh DA: Targeted antiangiogenic therapy for cancer using Vitaxin: a humanized monoclonal antibody to the integrin alphavbeta3. Clin Cancer Res. 6:3056–3061. 2000.PubMed/NCBI
51.	Burke PA, DeNardo SJ, Miers LA, Lamborn KR, Matzku S and DeNardo GL: Cilengitide targeting of alpha(v)beta(3) integrin receptor synergizes with radioimmunotherapy to increase efficacy and apoptosis in breast cancer xenografts. Cancer Res. 62:4263–4272. 2002.PubMed/NCBI
52.	Eskens FA, Dumez H, Hoekstra R, et al: Phase I and pharmacokinetic study of continuous twice weekly intravenous administration of cilengitide (EMD 121974), a novel inhibitor of the integrins alphavbeta3 and alphavbeta5 in patients with advanced solid tumours. Eur J Cancer. 39:917–926. 2003. View Article : Google Scholar
53.	Smith JW: Cilengitide Merck. Curr Opin Investig Drugs. 4:741–745. 2003.
54.	Miller WH, Bondinell WE, Cousins RD, et al: Orally bioavailable nonpeptide vitronectin receptor antagonists with efficacy in an osteoporosis model. Bioorg Med Chem Lett. 9:1807–1812. 1999. View Article : Google Scholar : PubMed/NCBI
55.	Kerr JS, Wexler RS, Mousa SA, et al: Novel small molecule alpha v integrin antagonists: comparative anti-cancer efficacy with known angiogenesis inhibitors. Anticancer Res. 19:959–968. 1999.PubMed/NCBI
56.	Freimuth P: A human cell line selected for resistance to adenovirus infection has reduced levels of the virus receptor. J Virol. 70:4081–4085. 1996.PubMed/NCBI
57.	Huang S, Kamata T, Takada Y, Ruggeri ZM and Nemerow GR: Adenovirus interaction with distinct integrins mediates separate events in cell entry and gene delivery to hematopoietic cells. J Virol. 70:4502–4508. 1996.PubMed/NCBI
58.	Goldman MJ and Wilson JM: Expression of alpha v beta 5 integrin is necessary for efficient adenovirus-mediated gene transfer in the human airway. J Virol. 69:5951–5958. 1995.PubMed/NCBI
59.	Bergelson JM, Cunningham JA, Droguett G, et al: Isolation of a common receptor for coxsackie b viruses and adenoviruses 2 and 5. Science. 275:1320–1323. 1997. View Article : Google Scholar : PubMed/NCBI
60.	Wickham TJ, Filardo EJ, Cheresh DA and Nemerow GR: Integrin alpha v beta 5 selectively promotes adenovirus-mediated cell membrane permeabilization. J Cell Biol. 127:257–264. 1994. View Article : Google Scholar : PubMed/NCBI
61.	Bai M, Harfe B and Freimuth P: Mutations that alter an arg-gly-asp (rgd) sequence in the adenovirus type 2 penton base protein abolish its cell-rounding activity and delay virus reproduction in flat cells. J Virol. 67:5198–5205. 1993.PubMed/NCBI
62.	Belin MT and Boulanger P: Involvement of cellular adhesion sequences in the attachment of adenovirus to the HeLa cell surface. J Gen Virol. 74:1485–1497. 1993. View Article : Google Scholar : PubMed/NCBI
63.	Wickham TJ, Mathias P, Cheresh DA and Nemerow GR: Integrins alpha v beta 3 and alpha v beta 5 promote adenovirus internalization but not virus attachment. Cell. 73:309–319. 1993. View Article : Google Scholar : PubMed/NCBI
64.	Miller CR, Buchsbaum DJ, Reynolds PN, et al: Differential susceptibility of primary and established human glioma cells to adenovirus infection: targeting via the epidermal growth factor receptor achieves fiber receptor-independent gene transfer. Cancer Res. 58:5738–5748. 1998.
65.	Huang S, Endo RI and Nemerow GR: Upregulation of integrins alpha v beta 3 and alpha v beta 5 on human monocytes and T lymphocytes facilitates adenovirus-mediated gene delivery. J Virol. 69:2257–2263. 1995.PubMed/NCBI
66.	Douglas JT, Kim M, Sumerel LA, Carey DE and Curiel DT: Efficient oncolysis by a replicating adenovirus (Ad) in vivo is critically dependent on tumor expression of primary Ad receptors. Cancer Res. 61:813–817. 2001.PubMed/NCBI
67.	Russell WC: Update on adenovirus and its vectors. J Gen Virol. 81:2573–2604. 2000.PubMed/NCBI
68.	Kelly FJ, Miller CR, Buchsbaum DJ, Gomez-Navarro J, Barnes MN, Alvarez RD and Curiel DT: Selectivity of TAG-72-targeted adenovirus gene transfer to primary ovarian carcinoma cells versus autologous mesothelial cells in vitro. Clin Cancer Res. 6:4323–4333. 2000.PubMed/NCBI
69.	Vanderkwaak TJ, Wang M, Gomez-Navarro J, et al: An advanced generation of adenoviral vectors selectively enhances gene transfer for ovarian cancer gene therapy approaches. Gynecol Oncol. 74:227–234. 1999. View Article : Google Scholar : PubMed/NCBI
70.	Kasono K, Blackwell JL, Douglas JT, et al: Selective gene delivery to head and neck cancer cells via an integrin targeted adenoviral vector. Clin Cancer Res. 5:2571–2579. 1999.PubMed/NCBI
71.	Li Y, Pong RC, Bergelson JM, et al: Loss of adenoviral receptor expression in human bladder cancer cells: a potential impact on the efficacy of gene therapy. Cancer Res. 59:325–330. 1999.PubMed/NCBI
72.	Hemmi S, Geertsen R, Mezzacasa A, Peter I and Dummer R: The presence of human coxsackievirus and adenovirus receptor is associated with efficient adenovirus-mediated transgene expression in human melanoma cell cultures. Hum Gene Ther. 9:2363–2373. 1998. View Article : Google Scholar : PubMed/NCBI
73.	Fechner H, Wang X, Wang H, et al: Trans-complementation of vector replication versus coxsackie-adenovirus-receptor overexpression to improve transgene expression in poorly permissive cancer cells. Gene Ther. 7:1954–1968. 2000. View Article : Google Scholar
74.	Cripe TP, Dunphy EJ, Holub AD, et al: Fiber knob modifications overcome low, heterogeneous expression of the coxsackievirusadenovirus receptor that limits adenovirus gene transfer and oncolysis for human rhabdomyosarcoma cells. Cancer Res. 61:2953–2960. 2001.PubMed/NCBI
75.	Krasnykh V, Belousova N, Korokhov N, Mikheeva G and Curiel DT: Genetic targeting of an adenovirus vector via replacement of the fiber protein with the phage t4 fibritin. J Virol. 75:4176–4183. 2001. View Article : Google Scholar : PubMed/NCBI
76.	Goldman CK, Rogers BE, Douglas JT, et al: Targeted gene delivery to Kaposi’s sarcoma cells via the fibroblast growth factor receptor. Cancer Res. 57:1447–1451. 1997.
77.	Douglas JT, Rogers BE, Rosenfeld ME, Michael SI, Feng M and Curiel DT: Targeted gene delivery by tropism-modified adenoviral vectors. Nat Biotechnol. 14:1574–1578. 1996. View Article : Google Scholar : PubMed/NCBI
78.	Stevenson SC, Rollence M, Marshall-Neff J and McClelland A: Selective targeting of human cells by a chimeric adenovirus vector containing a modified fiber protein. J Virol. 71:4782–4790. 1997.PubMed/NCBI
79.	Von Seggern DJ, Huang S, Fleck SK, Stevenson SC and Nemerow GR: Adenovirus vector pseudotyping in fiber-expressing cell lines: improved transduction of Epstein-barr virus-transformed B cells. J Virol. 74:354–362. 2000.PubMed/NCBI
80.	Wu H, Seki T, Dmitriev I, Uil T, Kashentseva E, Han T and Curiel DT: Double modification of adenovirus fiber with RGD and polylysine motifs improves coxsackievirus-adenovirus receptor-independent gene transfer efficiency. Hum Gene Ther. 13:1647–1653. 2002. View Article : Google Scholar
81.	Asaoka K, Tada M, Sawamura Y, Ikeda J and Abe H: Dependence of efficient adenoviral gene delivery in malignant glioma cells on the expression levels of the coxsackievirus and adenovirus receptor. J Neurosurg. 92:1002–1008. 2000. View Article : Google Scholar : PubMed/NCBI
82.	Grill J, van Beusechem VW, van Der Valk P, et al: Combined targeting of adenoviruses to integrins and epidermal growth factor receptors increases gene transfer into primary glioma cells and spheroids. Clin Cancer Res. 7:641–650. 2001.PubMed/NCBI
83.	Kanerva A, Wang M, Bauerschmitz GJ, et al: Gene transfer to ovarian cancer versus normal tissues with fiber-modified adenoviruses. Mol Ther. 5:695–704. 2002. View Article : Google Scholar : PubMed/NCBI
84.	Suzuki K, Fueyo J, Krasnykh V, Reynolds PN, Curiel DT and Alemany R: A conditionally replicative adenovirus with enhanced infectivity shows improved oncolytic potency. Clin Cancer Res. 7:120–126. 2001.PubMed/NCBI
85.	Bauerschmitz GJ, Lam JT, Kanerva A, et al: Treatment of ovarian cancer with a tropism modified oncolytic adenovirus. Cancer Res. 62:1266–1270. 2002.PubMed/NCBI
86.	Mathis JM, Stoff-Khalili MA and Curiel DT: Oncolytic adenoviruses – selective retargeting to tumor cells. Oncogene. 24:7775–7791. 2005.
87.	Vigne E, Mahfouz I, Dedieu JF, Brie A, Perricaudet M and Yeh P: RGD inclusion in the hexon monomer provides adenovirus type 5-based vectors with a fiber knob-independent pathway for infection. J Virol. 73:5156–5161. 1999.PubMed/NCBI
88.	Wu H, Han T, Lam JT, et al: Preclinical evaluation of a class of infectivity-enhanced adenoviral vectors in ovarian cancer gene therapy. Gene Ther. 11:874–878. 2004. View Article : Google Scholar : PubMed/NCBI
89.	Borovjagin AV, Krendelchtchikov A, Ramesh N, Yu DC, Douglas JT and Curiel DT: Complex mosaicism is a novel approach to infectivity enhancement of adenovirus type 5-based vectors. Cancer Gene Ther. 12:475–486. 2005.PubMed/NCBI
90.	Hesse A, Kosmides D, Kontermann RE and Nettelbeck DM: Tropism modification of adenovirus vectors by peptide ligand insertion into various positions of the adenovirus serotype 41 short-fiber knob domain. J Virol. 81:2688–2699. 2007. View Article : Google Scholar
91.	Page JG, Tian B, Schweikart K, et al: Identifying the safety profile of a novel infectivity-enhanced conditionally replicative adenovirus, Ad5-delta24-RGD, in anticipation of a phase I trial for recurrent ovarian cancer. Am J Obstet Gynecol. 196(389): e9–10. 2007.
92.	Parker AL, Waddington SN, Nicol CG, et al: Multiple vitamin k-dependent coagulation zymogens promote adenovirus-mediated gene delivery to hepatocytes. Blood. 108:2554–2561. 2006. View Article : Google Scholar : PubMed/NCBI
93.	Blackwell JL, Li H, Gomez-Navarro J, et al: Using a tropismmodified adenoviral vector to circumvent inhibitory factors in ascites fluid. Hum Gene Ther. 11:1657–1669. 2000. View Article : Google Scholar : PubMed/NCBI
94.	Elkas J, Baldwin R, Pegram M, Tseng Y and Karlan B: Immunoglobulin in ovarian cancer ascites inhibits viral infection: implications for adenoviral-mediated gene therapy. Gynecol Oncol. 72:4561999.
95.	Kanerva A, Mikheeva GV, Krasnykh V, et al: Targeting adenovirus to the serotype 3 receptor increases gene transfer efficiency to ovarian cancer cells. Clin Cancer Res. 8:275–280. 2002.PubMed/NCBI
96.	Yu W and Fang H: Clinical trials with oncolytic adenovirus in China. Curr Cancer Drug Targets. 7:141–148. 2007. View Article : Google Scholar : PubMed/NCBI
97.	Marshall E: Gene therapy death prompts review of adenovirus vector. Science. 286:2244–2245. 1999. View Article : Google Scholar : PubMed/NCBI
98.	Beardsley T: Gene therapy setback. Sci Am. 282:36–37. 2000. View Article : Google Scholar
99.	Jenks S: Gene therapy death – ‘Everyone has to share in the guilt’. J Natl Cancer Inst. 92:98–100. 2000.
100.	Miller HI: Gene therapy on trial. Science. 287:591–592. 2000. View Article : Google Scholar
101.	Raper SE, Yudkoff M, Chirmule N, et al: A pilot study of in vivo liver-directed gene transfer with an adenoviral vector in partial ornithine transcarbamylase deficiency. Hum Gene Ther. 13:163–175. 2002. View Article : Google Scholar : PubMed/NCBI
102.	Shirakawa T: The current status of adenovirus-based cancer gene therapy. Mol Cells. 25:462–466. 2008.PubMed/NCBI
103.	Barnes MN, Coolidge CJ, Hemminki A, Alvarez RD and Curiel DT: Conditionally replicative adenoviruses for ovarian cancer therapy. Mol Cancer Ther. 1:435–439. 2002.PubMed/NCBI
104.	Young A and McNeish IA: Oncolytic adenoviral gene therapy in ovarian cancer: why we are not wasting our time. Future Oncol. 5:339–357. 2009. View Article : Google Scholar : PubMed/NCBI
105.	O’Shea CC, Johnson L, Bagus B, et al: Late viral RNA export, rather than p53 inactivation, determines Onyx-015 tumor selectivity. Cancer Cell. 6:611–623. 2004.PubMed/NCBI
106.	Lieber A, He CY, Meuse L, Schowalter D, Kirillova I, Winther B and Kay MA: The role of Kupffer cell activation and viral gene expression in early liver toxicity after infusion of recombinant adenovirus vectors. J Virol. 71:8798–8807. 1997.PubMed/NCBI
107.	Tao N, Gao GP, Parr M, et al: Sequestration of adenoviral vector by Kupffer cells leads to a nonlinear dose response of transduction in liver. Mol Ther. 3:28–35. 2001. View Article : Google Scholar : PubMed/NCBI
108.	Wolff G, Worgall S, van Rooijen N, Song WR, Harvey BG and Crystal RG: Enhancement of in vivo adenovirus-mediated gene transfer and expression by prior depletion of tissue macrophages in the target organ. J Virol. 71:624–629. 1997.PubMed/NCBI
109.	Alemany R and Curiel DT: CAR-binding ablation does not change biodistribution and toxicity of adenoviral vectors. Gene Ther. 8:1347–1353. 2001. View Article : Google Scholar : PubMed/NCBI
110.	Smith TA, Idamakanti N, Rollence ML, et al: Adenovirus serotype 5 fiber shaft influences in vivo gene transfer in mice. Hum Gene Ther. 14:777–787. 2003. View Article : Google Scholar : PubMed/NCBI
111.	Shayakhmetov DM, Gaggar A, Ni S, Li ZY and Lieber A: Adenovirus binding to blood factors results in liver cell infection and hepatotoxicity. J Virol. 79:7478–7491. 2005. View Article : Google Scholar : PubMed/NCBI
112.	Kalyuzhniy O, Di Paolo NC, Silvestry M, Hofherr SE, Barry MA, Stewart PL and Shayakhmetov DM: Adenovirus serotype 5 hexon is critical for virus infection of hepatocytes in vivo. Proc Natl Acad Sci USA. 105:5483–5488. 2008. View Article : Google Scholar : PubMed/NCBI
113.	Waddington SN, McVey JH, Bhella D, et al: Adenovirus serotype 5 hexon mediates liver gene transfer. Cell. 132:397–409. 2008. View Article : Google Scholar : PubMed/NCBI
114.	Alvarez RD, Barnes MN, Gomez-Navarro J, et al: A cancer gene therapy approach utilizing an anti-erbb-2 single-chain antibody-encoding adenovirus (Ad21): a phase I trial. Clin Cancer Res. 6:3081–3087. 2000.PubMed/NCBI
115.	Alvarez RD, Gomez-Navarro J, Wang M, et al: Adenoviral-mediated suicide gene therapy for ovarian cancer. Mol Ther. 2:524–530. 2000. View Article : Google Scholar : PubMed/NCBI
116.	Hasenburg A, Tong XW, Rojas-Martinez A, et al: Thymidine kinase gene therapy with concomitant topotecan chemotherapy for recurrent ovarian cancer. Cancer Gene Ther. 7:839–844. 2000. View Article : Google Scholar : PubMed/NCBI
117.	Alvarez RD and Curiel DT: A phase I study of recombinant adenovirus vector-mediated delivery of an anti-erbb-2 single-chain (sFv) antibody gene for previously treated ovarian and extraovarian cancer patients. Hum Gene Ther. 8:229–242. 1997. View Article : Google Scholar
118.	Buller RE, Shahin MS, Horowitz JA, et al: Long term follow-up of patients with recurrent ovarian cancer after Ad p53 gene replacement with SCH 58500. Cancer Gene Ther. 9:567–572. 2002. View Article : Google Scholar : PubMed/NCBI
119.	Muller C, Coleman RL, Rogers P, et al: Phase I intraperitoneal p53 gene transfer in ovarian cancer. American Society of Clinical Oncology. 2001.
120.	Kanerva A, Bauerschmitz GJ, Yamamoto M, et al: A cyclooxygenase-2 promoter-based conditionally replicating adenovirus with enhanced infectivity for treatment of ovarian adenocarcinoma. Gene Ther. 11:552–559. 2004. View Article : Google Scholar : PubMed/NCBI
121.	Dmitriev IP, Kashentseva EA and Curiel DT: Engineering of adenovirus vectors containing heterologous peptide sequences in the C terminus of capsid protein IX. J Virol. 76:6893–6899. 2002. View Article : Google Scholar : PubMed/NCBI
122.	Vellinga J, Rabelink MJ, Cramer SJ, et al: Spacers increase the accessibility of peptide ligands linked to the carboxyl terminus of adenovirus minor capsid protein IX. J Virol. 78:3470–3479. 2004. View Article : Google Scholar : PubMed/NCBI