Noninvasive dual modality in vivo monitoring of the persistence and potency of a tumor targeted conditionally replicating adenovirus

• Published in: Gene therapy Vol. 12; no. 1; pp. 87 - 94
• Main Authors: KANERVA, A, ZINN, K. R, ALFTHAN, H, STENMAN, U.-H, CURIEL, D. T, HEMMINKI, A, PENG, K.-W, RANKI, T, KANGASNIEMI, L, CHAUDHURI, T. R, DESMOND, R. A, WANG, M, TAKAYAMA, K, HAKKARAINEN, T
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 2005
• Subjects: Adenocarcinoma - blood; Adenocarcinoma - therapy; Adenocarcinoma - virology; Adenoviridae - genetics; Adenoviridae - physiology; Adenovirus; Adenoviruses; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Applied cell therapy and gene therapy; Biological and medical sciences; Biomarkers, Tumor - blood; Biotechnology; Cancer; Carcinoembryonic Antigen - blood; Carcinoembryonic Antigen - genetics; Care and treatment; Female; Fundamental and applied biological sciences. Psychology; Gene therapy; Genetic aspects; Genetic Therapy - methods; Genetic Vectors - administration & dosage; Genetic Vectors - genetics; Health aspects; Health. Pharmaceutical industry; Humans; Industrial applications and implications. Economical aspects; Medical sciences; Methods; Mice; Mice, SCID; Ovarian Neoplasms - blood; Ovarian Neoplasms - therapy; Ovarian Neoplasms - virology; Physiological aspects; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Treatment Outcome; Virus Replication; Finland; Adenoviridae; virus replication; Virus; Persistence; In vivo; ovarian neoplasms; Surveillance; Imaging; adenovirus; Replication; Tumor; Gene therapy; Vector; Monitoring
• ISSN: 0969-7128; 1476-5462
• DOI: 10.1038/sj.gt.3302387

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.