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

Gene Therapy volume 12, pages 87–94 (2005)Cite this article

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.

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Acknowledgements

This work was supported by the Sohlberg Foundation, Sigrid Juselius Foundation, Emil Aaltonen Foundation, Maud Kuistila Foundation, Finnish Medical Foundation Duodecim, Academy of Finland, Finnish Cancer Society, Biocentrum Helsinki, Biomedicum Helsinki Foundation, Ida Montin Foundation, University of Helsinki Internal Funds, HUCH Research Funds, Research and Science Foundation of Farmos, Instrumentarium Research Fund, an unrestricted grant from AstraZeneca, and the NIH grants (R01 CA94084, R01 CA83821, P50 CA83591, R01 CA93796).

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Authors and Affiliations

  1. Cancer Gene Therapy Group, Rational Drug Design, Biomedicum Helsinki, University of Helsinki, Finland

    A Kanerva, T Ranki, L Kangasniemi & A Hemminki

  2. Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland

    A Kanerva & A Hemminki

  3. Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Helsinki, Finland

    A Kanerva, H Alfthan & U-H Stenman

  4. Department of Radiology, University of Alabama at Birmingham, Birmingham, AL, USA

    K R Zinn & T R Chaudhuri

  5. Molecular Medicine Program, Mayo Clinic, Rochester, MN, USA

    K-W Peng

  6. Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA

    R A Desmond

  7. Division of Human Gene Therapy, Departments of Medicine, Pathology and Surgery, and the Gene Therapy Center, University of Alabama at Birmingham, Birmingham, AL, USA

    M Wang & D T Curiel

  8. Research Institute for Diseases of the Chest, Kyushu University, Japan

    K Takayama

  9. Department of Biotechnology and Molecular Medicine, AI Virtanen Institute for Molecular Sciences, University of Kuopio, Kuopio, Finland

    T Hakkarainen

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  1. A Kanerva
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  2. K R Zinn
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  3. K-W Peng
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  4. T Ranki
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  8. M Wang
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  11. H Alfthan
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  12. U-H Stenman
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  13. D T Curiel
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  14. A Hemminki
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Kanerva, A., Zinn, K., Peng, KW. et al. Noninvasive dual modality in vivo monitoring of the persistence and potency of a tumor targeted conditionally replicating adenovirus. Gene Ther 12, 87–94 (2005). https://doi.org/10.1038/sj.gt.3302387

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  • DOI: https://doi.org/10.1038/sj.gt.3302387

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