1. ¹Cancer Gene Therapy Group, Rational Drug Design, Biomedicum Helsinki, University of Helsinki, Finland
2. ²Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland
3. ³Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Helsinki, Finland
4. ⁴Department of Radiology, University of Alabama at Birmingham, Birmingham, AL, USA
5. ⁵Molecular Medicine Program, Mayo Clinic, Rochester, MN, USA
6. ⁶Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
7. ⁷Division of Human Gene Therapy, Departments of Medicine, Pathology and Surgery, and the Gene Therapy Center, University of Alabama at Birmingham, Birmingham, AL, USA
8. ⁸Research Institute for Diseases of the Chest, Kyushu University, Japan
9. ⁹Department of Biotechnology and Molecular Medicine, AI Virtanen Institute for Molecular Sciences, University of Kuopio, Kuopio, Finland

Correspondence: Dr A Hemminki, Rational Drug Design, Biomedicum Helsinki, Department of Oncology, Helsinki University Central Hospital, PO Box 63 (Haartmaninkatu 8), 00014 University of Helsinki, Finland

Received 21 November 2003; Accepted 3 August 2004; Published online 23 September 2004.

Abstract

In clinical trials with cancer patients, the safety of conditionally replicating adenoviruses (CRAds) has been good. However, marginal data are available on the persistence or antitumor efficacy of these agents. The oncolytic potency of CRAds is determined by their capacity for entering target cells. Consequently, we constructed a retargeted CRAd featuring a secreted marker protein, soluble human carcinoembryogenic antigen (hCEA), which can be measured in growth medium or plasma. We found that virus replication closely correlated with hCEA secretion both in vitro and in vivo. Further, antitumor efficacy and the persistence of the virus could be deduced from plasma hCEA levels. Finally, using in vivo bioluminescence imaging, we were able to detect effective tumor cell killing by the virus, which led to enhanced therapeutic efficacy.