Journal
GENE THERAPY
Volume 12, Issue 1, Pages 87-94Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.gt.3302387
Keywords
adenovirus; ovarian neoplasms; virus replication; imaging
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Funding
- NCI NIH HHS [R01 CA93796, R01 CA83821, P50 CA83591, R01 CA94084] Funding Source: Medline
- NATIONAL CANCER INSTITUTE [R01CA093796, R01CA083821, R01CA094084, P50CA083591] Funding Source: NIH RePORTER
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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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