Depósito Académico >
CIMA (Centro de Investigación Médica Aplicada) >
Área de Terapia génica y Hepatología >
Inmunología terapia génica >
DA - CIMA - Terapia génica y Hepatología - Inmunología terapia génica - Artículos de revista >
Please use this identifier to cite or link to this item:
|Title: ||Anti-ICAM-2 monoclonal antibody synergizes with intratumor gene transfer of interleukin-12 inhibiting activation-induced T-cell death|
|Author(s) : ||Melero, I. (Ignacio)|
Gabari, I. (Izaskun)
Tirapu, I. (Íñigo)
Arina, A. (Ainhoa)
Mazzolini, G. (Guillermo)
Baixeras, E. (Elena)
Feijoo, E. (Esperanza)
Alfaro, C. (Carlos)
Qian, C. (Cheng)
Prieto, J. (Jesús)
|Issue Date: ||2003|
|Publisher: ||American Association for Cancer Research|
|Citation: ||Melero I, Gabari I, Tirapu I, Arina A, Mazzolini G, Baixeras E, et al. Anti-ICAM-2 monoclonal antibody synergizes with intratumor gene transfer of interleukin-12 inhibiting activation-induced T-cell death. Clin Cancer Res 2003 Sep 1;9(10 Pt 1):3546-3554.|
|Keywords: ||Antibodies, Monoclonal/chemistry|
Cell Adhesion Molecules/chemistry
Cell Adhesion Molecules/immunology
Gene Transfer Techniques
Systemic treatment with an anti-ICAM-2 monoclonal antibody (mAb; EOL4G8) eradicates certain established mouse tumors through a mechanism dependent on the potentiation of a CTL-mediated response. However, well-established tumors derived from the MC38 colon carcinoma cell line were largely refractory to this treatment as well as to intratumor injection of a recombinant adenovirus encoding interleukin-12 (IL-12; AdCMVIL-12). We sought to design combined therapy strategies with AdCMVIL-12 plus anti-ICAM-2 mAbs and to identify their mechanism of action.
Analysis of antitumor and toxic effects were performed with C57BL/6 mice bearing established MC38 tumors. Anti-ovalbumin T-cell receptor transgenic mice and tumors transfected with this antigen were used for in vitro and in vivo studies on activation-induced cell death (AICD) of CD8(+) T cells.
Combined treatment with various systemic doses of EOL4G8 mAb plus intratumor injection of AdCMVIL-12 induced complete regression of MC38 tumors treated 7 days after implantation. Unfortunately, most of such mice succumbed to a systemic inflammatory syndrome that could be prevented if IFN-gamma activity were neutralized once tumors had been rejected. Importantly, dose reduction of EOL4G8 mAb opened a therapeutic window (complete cure of 9 of 18 cases without toxicity). We also show that ICAM-2 ligation by EOL4G8 mAb on activated CTLs prevents AICD, thus extending IFN-gamma production.
Combination of intratumor gene transfer of IL-12and systemic anti-ICAM-2 mAb display synergistic therapeutic and toxic effects. CTL life extension resulting from AICD inhibition by anti-ICAM-2 mAbs is the plausible mechanism of action.|
|Publisher version (URL): ||http://clincancerres.aacrjournals.org/content/9/10/3546|
|Appears in Collections:||DA - Medicina - Medicina Interna - Artículos de revista|
DA - CIMA - Terapia génica y Hepatología - Inmunología terapia génica - Artículos de revista
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.