Intratumoural administration of dendritic cell: Hostile environment and help by gene therapy

Eduardo Huarte, Iñigo Tirapu, Ainhoa Arina, María Vera, Carlos Alfaro, Oihana Murillo, Belén Palencia, Victoria Busto, Verónica Marín, Guillermo Mazzolini, Ignacio Melero

Research output: Contribution to journalReview article

10 Scopus citations

Abstract

Like paratroopers in special operations, dendritic cells (DCs) can be deployed behind the enemy borders of malignant tissue to ignite an antitumour immune response. 'Cross-priming T cell responses' is the code name for their mission, which consists of taking up antigen from transformed cells or their debris, migrating to lymphoid tissue ferrying the antigenic cargo, and meeting specific T cells. This must be accomplished in such an immunogenic manner that specific T lymphocytes would mount a robust enough response as to fully reject the malignancy. To improve their immunostimulating activity, local gene therapy can be very beneficial, either by transfecting DCs with genes enhancing their performance, or by preparing tumour tissue with proinflammatory mediators. In addition, endogenous DCs from the tumour host can be attracted into the malignant tissue following transfection of certain chemokine genes into tumour cells. On their side, tumour stroma and malignant cells set up a hostile immunosuppressive environment for artificially released or attracted DCs. This milieu is usually rich in transforming growth factor-β, vascular endothelial growth factor, and IL-10, -6 and -8, among other substances that diminish DC performance. Several molecular strategies are being devised to interfere with the immunosuppressive actions of these substances and to further enhance the level of anticancer immunity achieved after artificial release of DCs intratumourally.

Original languageEnglish (US)
Pages (from-to)7-22
Number of pages16
JournalExpert opinion on biological therapy
Volume5
Issue number1
DOIs
StatePublished - Jan 1 2005

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Keywords

  • Anticancer
  • Delivery
  • Dendritic cells
  • Gene therapy
  • Intratumoural administration

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry

Cite this

Huarte, E., Tirapu, I., Arina, A., Vera, M., Alfaro, C., Murillo, O., Palencia, B., Busto, V., Marín, V., Mazzolini, G., & Melero, I. (2005). Intratumoural administration of dendritic cell: Hostile environment and help by gene therapy. Expert opinion on biological therapy, 5(1), 7-22. https://doi.org/10.1517/14712598.5.1.7