TY - JOUR
T1 - Intratumoural administration of dendritic cell
T2 - Hostile environment and help by gene therapy
AU - Huarte, Eduardo
AU - Tirapu, Iñigo
AU - Arina, Ainhoa
AU - Vera, María
AU - Alfaro, Carlos
AU - Murillo, Oihana
AU - Palencia, Belén
AU - Busto, Victoria
AU - Marín, Verónica
AU - Mazzolini, Guillermo
AU - Melero, Ignacio
N1 - Funding Information:
Grant support: grants from MCYT (SAF 02/0373), FIS (PI031253), Redes Temáticas de Investigación Coopera-tiva (RETICs, C03/10 and C03/02), Departamento de Salud y Departamento de Educación del Gobierno de Navarra and ‘UTE-project CIMA’. Scholarships are from Ministerio de Educación (IT) and FIS-BEFI (AA). The authors would like to acknowledge long-lasting collaborations and helpful scientific discussions with Drs Prieto, Lasarte, Sarobe, Ruiz, Qian, Sangro and Fortes, as well as the contribution of former collaborators M Duarte, E Feijoo and M Rodriguez-Calvillo.
PY - 2005/1
Y1 - 2005/1
N2 - 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.
AB - 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.
KW - Anticancer
KW - Delivery
KW - Dendritic cells
KW - Gene therapy
KW - Intratumoural administration
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UR - http://www.scopus.com/inward/citedby.url?scp=19944429072&partnerID=8YFLogxK
U2 - 10.1517/14712598.5.1.7
DO - 10.1517/14712598.5.1.7
M3 - Review article
C2 - 15709906
AN - SCOPUS:19944429072
SN - 1471-2598
VL - 5
SP - 7
EP - 22
JO - Expert opinion on biological therapy
JF - Expert opinion on biological therapy
IS - 1
ER -