1. ¹Cancer Gene Therapy Group, Molecular Cancer Biology Program and Haartman Institute, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland
2. ²Department of Oncology and Huslab, Helsinki University Central Hospital, Helsinki, Finland
3. ³Düsseldorf University Medical Center, Department of Obstetrics and Gynecology, Heinrich-Heine University, Düsseldorf, Germany
4. ⁴Transplantation Laboratory, Helsinki University Central Hospital, Helsinki, Finland
5. ⁵Comprehensive Cancer Center, Biostatistics and Bioinformatics Unit, University of Alabama at Birmingham, Birmingham, AL, USA
6. ⁶Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Helsinki, Finland

Correspondence: Dr A Hemminki, Cancer Gene Therapy Group, Biomedicum Helsinki, Haartmaninkatu 8, 00290 Helsinki, Finland. E-mail: akseli.hemminki@helsinki.fi

Received 9 February 2007; Revised 19 February 2007; Accepted 20 February 2007; Published online 22 March 2007.

Abstract

Oncolytic viruses kill cancer cells by tumor-selective replication. Clinical data have established the safety of the approach but also the need of improvements in potency. Efficacy of oncolysis is linked to effective infection of target cells and subsequent productive replication. Other variables include intratumoral barriers, access to target cells, uptake by non-target organs and immune response. Each of these aspects relates to the location and degree of virus replication. Unfortunately, detection of in vivo replication has been difficult, labor intensive and costly and therefore not much studied. We hypothesized that by coinfection of a luciferase expressing E1-deleted virus with an oncolytic virus, both viruses would replicate when present in the same cell. Photon emission due to conversion of D-Luciferin is sensitive and penetrates tissues well. Importantly, killing of animals is not required and each animal can be imaged repeatedly. Two different murine xenograft models were used and intratumoral coinjections of luciferase encoding virus were performed with eight different oncolytic adenoviruses. In both models, we found significant correlation between photon emission and infectious virus production. This suggests that the system can be used for non-invasive quantitation of the amplitude, persistence and dynamics of oncolytic virus replication in vivo, which could be helpful for the development of more effective and safe agents.