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ONYX-411, a conditionally replicative oncolytic adenovirus, induces cell death in anaplastic thyroid carcinoma cell lines and suppresses the growth of xenograft tumors in nude mice

Abstract

Anaplastic thyroid carcinoma (ATC) is the most aggressive thyroid cancer variant, accounting for 1–2% of all cases, but 33% of deaths, and exhibiting an average life expectancy of 5 months. ATC is largely unresponsive to radioactive iodine, chemotherapy, external beam radiation or surgery, underscoring the need for new and effective therapies. We evaluated the therapeutic potential of an oncolytic adenovirus, ONYX-411, that replicates selectively in and kills cells with dysfunction of the retinoblastoma (RB) pathway. In the present study, we report that ONYX-411 is able to induce cell death in eight human anaplastic carcinoma cell lines in vitro. The cytopathic effect of the virus is specific to cells with RB dysfunction, which appears to be frequent in ATC. We confirmed the expression of the coxsackie adenovirus receptor, CAR, in all ATC cell lines, demonstrating the potentially universal application of this oncolytic viral therapy to ATC. In addition, the growth of xenograft tumors induced in athymic mice with the ARO and DRO cell lines was significantly reduced by ONYX-411 treatment. These results indicate that ONYX-411 can be a potential therapeutic agent for the treatment of ATC, rendering this class of conditionally replicating adenoviruses an attractive candidate for clinical trials.

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Acknowledgements

This work was supported by NIH Grant CA80117 (NLE), a generous donation from the Price Foundation, Florida Department of Health Bankhead-Coley grant (JAC) and a grant for rare cancers from Dr Ellis and Dona Brunton (JAC). We wish to extend their appreciation to Dr Lori Erickson for help with the interpretation of the hematoxylin and eosin-stained slides of ATC-xenografted tumors in nude mice. We are also indebted to Dr Henry J Hiddinga for assistance with the animal studies.

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Correspondence to N L Eberhardt.

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Reddi, H., Madde, P., Reichert-Eberhardt, A. et al. ONYX-411, a conditionally replicative oncolytic adenovirus, induces cell death in anaplastic thyroid carcinoma cell lines and suppresses the growth of xenograft tumors in nude mice. Cancer Gene Ther 15, 750–757 (2008). https://doi.org/10.1038/cgt.2008.44

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  • DOI: https://doi.org/10.1038/cgt.2008.44

Keywords

  • anaplastic thyroid carcinoma
  • ONYX-411
  • retinoblastoma dysfunction
  • novel therapeutic agent

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