title: Both HIV- and EIAV-based lentiviral vectors mediate gene delivery to pancreatic cancer cells and human pancreatic primary patient xenografts.
abstract: Few effective treatments for pancreatic cancer exist, especially for patients with advanced disease. Gene therapy alone, or combined with current treatments, offers an alternative approach. Here we examined the potential of primate and nonprimate lentivectors to mediate gene delivery to this cancer type. VSV-G pseudotyped lentivectors based on human immunodeficiency type-1 virus (HIV-1) and equine infectious anemia virus (EIAV), containing the enhanced green fluorescent protein (EGFP) reporter gene were prepared and characterized for titer and RNA content. Vector-mediated gene delivery was examined in five pancreatic cancer cell lines in vitro, and in MiaPaCa-2 cells as well as in five human primary patient biopsies xenografted subcutaneously in nude mice. While individual cell lines showed differential sensitivities to transduction with lentivectors, all cell lines were successfully transduced with both vector types. Similarly, both vectors transduced MiaPaCa-2 and all of the human primary patient xenografts. We observed 6-29% transduction with HIV-based vectors (n=3 xenografts) and 1.8-30% with EIAV-based vectors (n=4 xenografts). Long-term EIAV-mediated gene expression was recorded in cell lines for up to 6 months. We conclude that these vectors have potential as mediators of clinical gene therapy for pancreatic cancer treatment. Moreover, they are useful laboratory research tools for pancreatic cancer research.
authors.affiliation: Division of Surgery and Oncology, Royal Liverpool University Hospital, University of Liverpool, Liverpool, Merseyside L68 3GA, UK.
authors.forename: G
authors.initials: G
authors.lastname: Saraga
authors.forename: A
authors.initials: A
authors.lastname: Mafficini
authors.forename: P
authors.initials: P
authors.lastname: Ghaneh
authors.forename: C
authors.initials: C
authors.lastname: Sorio
authors.forename: E
authors.initials: E
authors.lastname: Costello
mesh_terms: D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D017931:DNA Primers; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006678:HIV / Q000235:genetics*; D006801:Humans; D004860:Infectious Anemia Virus, Equine / Q000235:genetics*; D051379:Mice; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D014161:Transduction, Genetic; D014407:Tumor Cells, Cultured
chemical_list: D017931:DNA Primers