title: A fiber-modified adenovirus co-expressing HSV-TK and Coli.NTR enhances antitumor activities in breast cancer cells.
abstract: Breast cancers especially in late and metastatic stages remain refractory to treatment despite advances in surgical techniques and chemotherapy. Suicide gene therapy based on adenoviral technology will be promising strategies for such advanced diseases. We previously showed that co-expression of herpes simplex virus thymidine kinase (HSV-TK) and Escherichia coli nitroreductase (Coli.NTR) by an hTERT-driven adenovirus vector resulted in additive anti-tumor effects in breast cancer cells in vitro and in vivo. As many tumor tissue and cancer cells express low level of coxsackie-adenovirus receptor (CAR), which is the functional receptor for the fiber protein of human adenovirus serotype 5 (Ad5), novel Ad5 vectors containing genetically modifi ed fiber are attractive vehicles for achieving targeted gene transfer and improving suicide gene expression in these cancer cells. In the present study, we first built a simplified Ad5 vector platform for fiber modification and quick detection for gene transfer. Then a fiber-modified adenovirus vector containing an RGD motif in the HI loop of the fiber knob was constructed. After recombined with HSV-TK and Coli.NTR gene, this fiber-modified Ad5 vector (Ad-RGD-hT-TK/NTR) was compared with that of our previously constructed Ad5 vector (Ad-hT-TK/NTR) for its therapeutic effects in human breast cancer cell lines. The anti-tumor activity of Ad-RGD-hT-TK/NTR was significantly enhanced compared with Ad-hT-TK/NTR both in vitro and in vivo. This new vector platform provided a robust and simplified approach for capsid modification, and the fiber-modified Ad5 with double suicide genes under the control of hTERT promoter would be a useful gene therapy strategy for breast cancer.
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University 2699 Qianjin Street, Changchun 130012, China ; Key Laboratory for Molecular Enzymology and Engineering, The Ministry of Education, School of Life Sciences, Jilin University 2699 Qianjin Street, Changchun 130012, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhan
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University 2699 Qianjin Street, Changchun 130012, China ; Key Laboratory for Molecular Enzymology and Engineering, The Ministry of Education, School of Life Sciences, Jilin University 2699 Qianjin Street, Changchun 130012, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Yu
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University 2699 Qianjin Street, Changchun 130012, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University 2699 Qianjin Street, Changchun 130012, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University 2699 Qianjin Street, Changchun 130012, China ; Key Laboratory for Molecular Enzymology and Engineering, The Ministry of Education, School of Life Sciences, Jilin University 2699 Qianjin Street, Changchun 130012, China.
authors.forename: Hai-Hong
authors.initials: HH
authors.lastname: Zhang
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University 2699 Qianjin Street, Changchun 130012, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University 2699 Qianjin Street, Changchun 130012, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Feng
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University 2699 Qianjin Street, Changchun 130012, China.
authors.forename: Ran-Shen
authors.initials: RS
authors.lastname: Geng
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University 2699 Qianjin Street, Changchun 130012, China ; Key Laboratory for Molecular Enzymology and Engineering, The Ministry of Education, School of Life Sciences, Jilin University 2699 Qianjin Street, Changchun 130012, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Kong
authors.affiliation: National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University 2699 Qianjin Street, Changchun 130012, China ; Key Laboratory for Molecular Enzymology and Engineering, The Ministry of Education, School of Life Sciences, Jilin University 2699 Qianjin Street, Changchun 130012, China.
authors.forename: Xiang-Hui
authors.initials: XH
authors.lastname: Yu
mesh_terms: D000256:Adenoviridae; D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology* / Q000821:virology; D045744:Cell Line, Tumor; D004926:Escherichia coli; D029968:Escherichia coli Proteins / Q000235:genetics*; D005260:Female; D005434:Flow Cytometry; D041722:Genes, Transgenic, Suicide / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D009601:Nitroreductases / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018139:Simplexvirus; D013937:Thymidine Kinase / Q000235:genetics*; D014764:Viral Proteins / Q000235:genetics / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
chemical_list: D029968:Escherichia coli Proteins; D014764:Viral Proteins; C116053:NfsA protein, E coli; D009601:Nitroreductases; D013937:Thymidine Kinase
keywords: Adenovirus; breast cancer; suicide gene