Scientific publications

Deletion of the E3-6.7K/gp19K region reduces the persistence of wild-type adenovirus in a permissive tumor model in Syrian hamsters

Bortolanza S, Bunuales M, Alzuguren P, Lamas O, Aldabe R, Prieto J, Hernandez-Alcoceba R.
Division of Hepatology and Gene Therapy, CIMA, Foundation for Applied Medical Research, School of Medicine, University of Navarra, Pamplona 31008, Spain.

Magazine: Cancer Gene Therapy

Date: Sep 1, 2009

Hepatology

A partial deletion of the adenovirus E3 region, comprising the overlapping 6.7K/gp19K genes, has been described for the incorporation of therapeutic genes in 'armed' oncolytic adenoviruses. This deletion allows the insertion of up to 2.5 kb genetic material into the virus and ensures strong expression of transgenes without reducing the replication and cytolytic potency of viruses in vitro. E3-gp19K and 6.7K proteins are involved in avoiding recognition and elimination of infected cells by the host immune system. Therefore, we have studied the effect of this deletion on the replication and transgene expression of the virus in immunocompetent models based on Syrian hamsters.

Tumors were established by intrahepatic injection of pancreatic cancer cells with moderate (HaP-T1, HP-1) or low (H2T) permissivity for adenovirus replication. The wild-type human adenovirus 5 (Ad5) or a modified version containing the luciferase gene in the E3-6.7K/gp19K locus (Ad-WTLuc) were injected intratumorally. We found that elimination of Ad-WTLuc was faster than Ad5 in HaP-T1 and HP-1 tumors. In contrast, no differences were observed when the same tumor was established in severely immunocompromised NOD-scid IL2Rgamma(null) mice. In addition, virus-mediated luciferase expression was more stable in these animals.

These results suggest that the lack of E3-6.7K/gp19K genes may accelerate the clearance of oncolytic adenoviruses in some immunocompetent tumor models.

CITATION  Cancer Gene Ther. 2009 Sep;16(9):703-12

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