Full metadata record
DC Field | Value | Language |
---|---|---|
dc.creator | Mazzolini, G. (Guillermo) | - |
dc.creator | Prieto, J. (Jesús) | - |
dc.creator | Melero, I. (Ignacio) | - |
dc.date.accessioned | 2012-04-23T10:20:47Z | - |
dc.date.available | 2012-04-23T10:20:47Z | - |
dc.date.issued | 2003 | - |
dc.identifier.citation | Mazzolini G, Prieto J, Melero I. Gene therapy of cancer with interleukin-12. Curr Pharm Des 2003;9(24):1981-1991. | es_ES |
dc.identifier.issn | 1873-4286 | - |
dc.identifier.uri | https://hdl.handle.net/10171/21740 | - |
dc.description.abstract | IL-12 has demonstrated remarkable antitumor activity when used directly as a recombinant protein or when different viral or non-viral vectors transfer its genes. At enhancing tumor immunity, IL-12 acts as a bridge between innate and adaptive immune responses due to its ability to induce proliferation and activation of NK, NKT, and T cells. In addition, IL-12 inhibits tumor angiogenesis mainly through IFN gamma-dependent production of the chemokine IP10. As a result, IL-12 can eliminate several types of tumors developed in rodents. Pre-clinical experience forecasted a quick and successful clinical translation, but the encouraging results observed in animals were not reproduced in patients. Moreover, unacceptable toxicity resulting from IFN gamma overproduction was observed in 2 renal carcinoma patients included in a phase II clinical trial that consisted in systemic administration of rIL-12. As a consequence, development of IL-12 as an antitumor agent was temporarily halted while the high expectations raised among clinicians faded away. Gene transfer methods are designed to confine IL-12 production in the tumor environment preventing systemic toxicity. Tumor cells, dendritic cells, or autologous fibroblasts have been transfected with recombinant adenoviruses or retroviruses to secrete IL-12 locally, showing good efficacy and safety profiles. IL-12 combination with other immunotherapy approaches synergizes to achieve even better results. Encouraging pilot clinical results have been recently obtained from the first phase I trial studying adenovirus mediated in vivo gene transfer of IL-12 into lesions of advanced cancer patients. Further improvements will follow from: i) increases in the efficacy of gene transduction; ii) development of tumor specific promoters; iii) development of regulatable and long-term expression vectors and iv) combination with other immunological and non-immunological anticancer therapies. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Bentham Science Publishers | es_ES |
dc.rights | info:eu-repo/semantics/closedAccess | - |
dc.subject | il-12 | es_ES |
dc.subject | Gene therapy | es_ES |
dc.subject | Cancer | es_ES |
dc.subject | Adenovirus | es_ES |
dc.subject | Dentritic cells | es_ES |
dc.subject | Mouse | es_ES |
dc.subject | Clinical trials | es_ES |
dc.title | Gene therapy of cancer with interleukin-12 | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.relation.publisherversion | http://bit.ly/IiZ5mm | es_ES |
dc.type.driver | info:eu-repo/semantics/article | es_ES |
Files in This Item:
There are no files associated with this item.
Statistics and impact
Items in Dadun are protected by copyright, with all rights reserved, unless otherwise indicated.