Publicações científicas

Genetic heterogeneity in the toxicity to systemic adenoviral gene transfer of interleukin-12

Mazzolini G, Narvaiza I, Pérez-Diez A, Rodriguez-Calvillo M, Qian C, Sangro B, Ruiz J, Prieto J, Melero I.
Gene Therapy Unit, Department of Internal Medicine, School of Medicine, University of Navarra, Irunlarrea, 1 (31080), Pamplona, Spain.

Revisão:Gene Therapy

Data: 1/Fev/2001

Imunologia e Imunoterapia [ES] Hepatologia

Despite the efficacy of IL-12 in cancer experimental models, clinical trials with systemic recombinant IL-12 showed unacceptable toxicity related to endogenous IFNgamma production. We report that systemic administration of a recombinant adenovirus encoding IL-12 (AdCMVmIL-12) has a dramatically different survival outcome in a number of mouse pure strains over a wide range of doses. For instance at 2.5 x 10(9) p.f.u., systemic AdCMVmIL-12 killed all C57BL/6 mice but spared all BALB/c mice.

Much higher IFNgamma concentrations in serum samples of C57BL/6 than in those from identically treated BALB/c were found. Causes for heterogeneous toxicity can be traced to differences among murine strains in the levels of gene transduction achieved in the liver, as assessed with adenovirus coding for reporter genes. In accordance, IL-12 serum concentrations are higher in susceptible mice. In addition, sera from C57BL/6 mice treated with AdCMVmIL-12 showed higher levels of IL-18, a well-known IFNgamma inducer. Interestingly, lethal toxicity in C57BL/6 mice was abolished by administration of blocking anti-IFNgamma mAbs and also by simultaneous depletion of T cells, NK cells, and macrophages.

These observations together with the great dispersion of IFNgamma produced by human PBMCs upon in vitro stimulation with IL-12, or infection with recombinant adenovirus encoding IL-12, suggest that patients might also show heterogeneous degrees of toxicity in response to IL-12 gene transfer.

CITAÇÃO DO ARTIGO  Gene Ther. 2001 Feb;8(4):259-67

talvezlhe interesse


A Clínica é o hospital privado com maiores recursos tecnológicos de Espanha, tudo num único centro.

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


Os profissionais da Clínica realizam um trabalho contínuo de investigação e formação, sempre em benefício do paciente.

Imagen profesionales de la Clínica Universidad de Navarra


Conheça porque é que somos diferentes em relação a outros centros sanitários. Qualidade, rapidez, comodidade e resultados.

Imagen del edificio de la Clínica Universidad de Navarra