Scientific publications

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 [SP], Prieto J, Peñuelas I [SP], Melero I [SP].
Gene Therapy and Hepatology Area, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain

Magazine: Molecular Therapy

Date: Apr 1, 2010

Radiology [SP] Nuclear Medicine [SP] Hepatology Immunology [SP]

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.

CITATION Mol Ther. 2010 Apr;18(4):754-65

you maybe interested

WHAT TECHNOLOGY
DO WE USE?

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

OUR
PROFESSIONALS

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

WHY CHOOSE
THE CLINICA?

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

Imagen del edificio de la Clínica Universidad de Navarra