Publicaciones científicas

Anti-ICAM-2 monoclonal antibody synergizes with intratumor gene transfer of interleukin-12 inhibiting activation-induced T-cell death

Melero I, Gabari I, Tirapu I, Arina A, Mazzolini G, Baixeras E, Feijoo E, Alfaro C, Qian C, Prieto J.
Centro de Investigación Médica Aplicada (CIMA), Facultad de Medicina, Gene Therapy Unit, Universidad de Navarra, 31008 Pamplona, Spain

Revista: Clinical Cancer Research

Fecha: 01/09/2003

Medicina Interna

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.

CITA DEL ARTÍCULO  Clin Cancer Res. 2003 Sep 1;9(10 Pt 1):3546-54



La Clínica es el hospital privado con mayor dotación tecnológica de España, todo en un único centro.

Imagen de un PET, tecnología de vanguardia en la Clínica Universidad de Navarra


Los profesionales de la Clínica realizan una labor continuada de investigación y formación, siempre en beneficio del paciente.

Imagen profesionales de la Clínica Universidad de Navarra


Conozca por qué somos diferentes a otros centros sanitarios. Calidad, rapidez, comodidad y resultados.

Imagen del edificio de la Clínica Universidad de Navarra