title: Identification and characterization of a novel peptide ligand of Tie2 for targeting gene therapy.
abstract: Tyrosine kinase with immunoglobulin and epidermal growth factor homology domain-2 (Tie2) has been considered as a rational target for gene therapy in solid tumors. In order to identify a novel peptide ligand of Tie2 for targeted gene therapy, we screened a phage display peptide library and identified a candidate peptide ligand NSLSNASEFRAPY (designated GA5). Binding assays and Scatchard analysis revealed that GA5 could specifically bind to Tie2 with a dissociation constant of 2.1x10(-8)M. In addition, we showed that GA5 was internalized into tumor cells highly expressing Tie2. In the biodistribution assay, (125)I-GA5 was mainly accumulated in SPC-A1 xenograft tumors that express Tie2. In gene delivery studies, GA5-conjugated polyethylenimine vector could achieve greater transgene transduction than non-targeted vectors both in vitro and in vivo. Tumor growth inhibition was observed in SPC-A1 xenograft-bearing mice that received eight intratumoral injections of GA5-polyethylenimine/p53 complexes in 3 weeks. The difference in tumor volume between the experiment and control groups was significant (P<0.05). Our results showed that GA5 is a potentially efficient targeting element for cancer gene or molecular therapy.
authors.affiliation: Department of Medical Oncology, Cancer Hospital of Fudan University, Shanghai 200032, China.
authors.forename: Xianghua
authors.initials: X
authors.lastname: Wu
authors.forename: Zonghai
authors.initials: Z
authors.lastname: Li
authors.forename: Ming
authors.initials: M
authors.lastname: Yao
authors.forename: Huamao
authors.initials: H
authors.lastname: Wang
authors.forename: Sumin
authors.initials: S
authors.lastname: Qu
authors.forename: Xianlian
authors.initials: X
authors.lastname: Chen
authors.forename: Jinjun
authors.initials: J
authors.lastname: Li
authors.forename: Ye
authors.initials: Y
authors.lastname: Sun
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Xu
authors.forename: Jianren
authors.initials: J
authors.lastname: Gu
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D018390:Gene Targeting / Q000379:methods*; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010455:Peptides / Q000235:genetics* / Q000627:therapeutic use*; D042787:Receptor, TIE-2 / Q000235:genetics* / Q000378:metabolism*; D014018:Tissue Distribution; D014213:Tretoquinol; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000627:therapeutic use
chemical_list: D010455:Peptides; D016159:Tumor Suppressor Protein p53; D042787:Receptor, TIE-2; D014213:Tretoquinol