Publicações científicas

Intensive pharmacological immunosuppression allows for repetitive liver gene transfer with recombinant adenovirus in nonhuman primates

Fontanellas A, Hervás-Stubbs S, Mauleón I, Dubrot J, Mancheño U, Collantes M, Sampedro A, Unzu C, Alfaro C, Palazón A, Smerdou C, Benito A [ES], Prieto J, Peñuelas I [ES], Melero I [ES].
Gene Therapy and Hepatology Area, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain

Revisão:Molecular Therapy

Data: 1/Abr/2010

Radiología [ES] Medicina Nuclear [ES] Hepatologia Imunologia e Imunoterapia [ES]

Repeated administration of gene therapies is hampered by host immunity toward vectors and transgenes. Attempts to circumvent antivector immunity include pharmacological immunosuppression or alternating different vectors and vector serotypes with the same transgene.

Our studies show that B-cell depletion with anti-CD20 monoclonal antibody and concomitant T-cell inhibition with clinically available drugs permits repeated liver gene transfer to a limited number of nonhuman primates with recombinant adenovirus. Adenoviral vector-mediated transfer of the herpes simplex virus type 1 thymidine kinase (HSV1-tk) reporter gene was visualized in vivo with a semiquantitative transgene-specific positron emission tomography (PET) technique, liver immunohistochemistry, and immunoblot for the reporter transgene in needle biopsies.

Neutralizing antibody and T cell-mediated responses toward the viral capsids were sequentially monitored and found to be repressed by the drug combinations tested. Repeated liver transfer of the HSV1-tk reporter gene with the same recombinant adenoviral vector was achieved in macaques undergoing a clinically feasible immunosuppressive treatment that ablated humoral and cellular immune responses.

This strategy allows measurable gene retransfer to the liver as late as 15 months following the first adenoviral exposure in a macaque, which has undergone a total of four treatments with the same adenoviral vector.

CITAÇÃO DO ARTIGO Mol Ther. 2010 Apr;18(4):754-65

talvezlhe interesse

QUE TECNOLOGIA UTILIZAMOS? 

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 NOSSOS
PROFISSIONAIS

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

RAZÕES PARA VIR
À CLÍNICA

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