title: Gene therapy approaches against cancer using in vivo and ex vivo gene transfer of interleukin-12.
abstract: IL-12 is an immunostimulatory cytokine with strong antitumor properties. Systemic administration of IL-12 in cancer patients led to severe toxic effects, prompting the development of gene therapy vectors able to express this cytokine locally in tumors. Both nonviral and viral vectors have demonstrated a high antitumor efficacy in preclinical tumor models. Some of these vectors, including DNA electroporation, adenovirus and ex vivo transduced dendritic cells, were tested in patients, showing low toxicity and moderate antitumor efficacy. IL-12 activity can be potentiated by molecules with immunostimulatory, antiangiogenic or cytotoxic activity. These combination therapies are of clinical interest because they could lower the threshold for IL-12 efficacy, increasing the therapeutic potential of gene therapy and preventing the toxicity mediated by this cytokine.
authors.affiliation: Division of Gene Therapy, CIMA, University of Navarra, Pamplona 31008 Spain.|Instituto de Investigación Sanitaria de Navarra, c/Irunlarrea 3, Pamplona 31008, Spain.
authors.forename: Ruben
authors.initials: R
authors.lastname: Hernandez-Alcoceba
authors.affiliation: Division of Gene Therapy, CIMA, University of Navarra, Pamplona 31008 Spain.|Instituto de Investigación Sanitaria de Navarra, c/Irunlarrea 3, Pamplona 31008, Spain.
authors.forename: Joanna
authors.initials: J
authors.lastname: Poutou
authors.affiliation: Division of Gene Therapy, CIMA, University of Navarra, Pamplona 31008 Spain.|Instituto de Investigación Sanitaria de Navarra, c/Irunlarrea 3, Pamplona 31008, Spain.
authors.forename: María Cristina
authors.initials: MC
authors.lastname: Ballesteros-Briones
authors.affiliation: Division of Gene Therapy, CIMA, University of Navarra, Pamplona 31008 Spain.|Instituto de Investigación Sanitaria de Navarra, c/Irunlarrea 3, Pamplona 31008, Spain.
authors.forename: Cristian
authors.initials: C
authors.lastname: Smerdou
mesh_terms: D000818:Animals; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics / Q000627:therapeutic use; D006801:Humans; D018664:Interleukin-12 / Q000235:genetics* / Q000276:immunology*; D009369:Neoplasms / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D014161:Transduction, Genetic / Q000379:methods*
chemical_list: D018664:Interleukin-12
keywords: IL-12; cancer; gene therapy; immunotherapy; nonviral vectors; viral vectors