Scientific publications

Intratumoral coinjection of two adenoviruses, one encoding the chemokine IFN-gamma-inducible protein-10 and another encoding IL-12, results in marked antitumoral synergy

Narvaiza I, Mazzolini G, Barajas M, Duarte M, Zaratiegui M, Qian C, Melero I, Prieto J.
Departments ofMedicine and Genetics, Facultad de Medicina, Universidad de Navarra, Pamplona, Spain

Magazine: Journal of Immunology

Date: Mar 15, 2000

Hepatology Immunology [SP]

We have constructed a recombinant defective adenovirus that expresses functional murine IFN-gamma-inducible protein-10 (IP-10) chemokine (AdCMVIP-10). Injection of AdCMVIP-10 into s.c. tumor nodules derived from the CT26 murine colorectal adenocarcinoma cell line displayed some antitumor activity but it was not curative in most cases.

Previous studies have shown that injection of similar s. c. CT26 tumor nodules with adenovirus-encoding IL-12 (AdCMVIL-12) induces tumor regression in nearly 70% of cases in association with generation of antitumor CTL activity. AdCMVIP-10 synergizes with the antitumor effect of suboptimal doses of AdCMVIL-12, reaching 100% of tumor eradication not only against injected, but also against distant noninjected tumor nodules. Colocalization of both adenoviruses at the same tumor nodule was required for the local and distant therapeutic effects. Importantly, intratumoral gene transfer with IL-12 and IP-10 generated a powerful tumor-specific CTL response in a synergistic fashion, while both CD4 and CD8 T cells appeared in the infiltrate of regressing tumors. Moreover, the antitumor activity of IP-10 plus IL-12 combined gene therapy was greatly diminished by simultaneous in vivo depletion of CD4+ and CD8+ T cells but was largely unaffected by single depletion of each T cell subset. An important role for NK cells was also suggested by asialo GM1 depletion experiments.

From a clinical point of view, the effects of IP-10 permit one to lower the required gene transfer level of IL-12, thus preventing dose-dependent IL-12-mediated toxicity while improving the therapeutic efficacy of the elicited antitumor response.

CITATION J Immunol. 2000 Mar 15;164(6):3112-22

you maybe interested


The Clínica is the greater private hospital with technological equipment of Spain, all in a single center.

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


The professionals of the Clínica perform continuous research and training, always to the benefit of the patient.

Imagen profesionales de la Clínica Universidad de Navarra


Learn why we are different from other healthcare centers. Quality, speed, comfort and results.

Imagen del edificio de la Clínica Universidad de Navarra