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Clinical trial of E1B-deleted adenovirus (dl1520) gene therapy for hepatocellular carcinoma

Cancer Gene Therapy volume 9, pages 254–259 (2002)Cite this article

Abstract

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. The prognosis of HCC is poor and current therapies are largely ineffective. Genetic abnormalities are commonly seen in HCC tumors particularly with inactivation of the p53 tumor suppressor. Gene therapy with E1B-deleted (dl1520) adenovirus could be of therapeutic value as it offers the potential of tumor growth control in patients with p53 mutation. Ten patients with posthepatitis cirrhosis and histologically proven HCC were enrolled into an open label, randomized prospective study. Randomization was to receive either percutaneous ethanol injection (control group) or dl1520. Toxicity and complications in the ethanol group were pain and fever, whereas in the gene therapy group complications were minimal. Grade I–II toxicity fever, stable performance status, and no significant rise in liver enzymes were observed in patients treated with dl1520. Analysis of patients' response to treatment in the gene therapy group showed one patient with a partial response and four patients with progressive disease. In the ethanol-treated group two patients had stable disease and three patients showed disease progression. In conclusion, this study showed that the adenovirus was well tolerated, but did not seem to offer significant tumor control. Although only a small number of patients were treated here it appears that more effective vectors are needed to achieve a useful clinical impact.

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Acknowledgements

We thank Professor Arnold Berk (California) for giving us the dl1520 and the Pedersen Foundation for financially supporting this work. We are grateful to VE Emons for electron microscopy.

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Authors and Affiliations

  1. Division of Surgery, Anaesthetics and Intensive Care, Imperial College School of Medicine, Hammersmith Hospital Campus, London, W12 ONN, UK

    Nagy Habib, Catherine Sarraf, Ragai Mitry, Roman Havlik, Joanna Nicholls & Steen Jensen

  2. Faculty of Medicine, Cairo University, Cairo, Egypt

    Hosny Salama, Ahmed Abd El Latif Abu Median & Rasha Ahmed Abd Al Aziz

  3. Department of Tropical Medicine, Faculty of Medicine, Cairo University, Cairo, Egypt

    Ilia Isac Anis

  4. Des Moines University, Des Moines, 50312, Iowa, USA

    Prem Seth, Jack Hartwigsen & Reva Bhushan

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  1. Nagy Habib
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  3. Ahmed Abd El Latif Abu Median
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Correspondence to Nagy Habib.

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Habib, N., Salama, H., Abd El Latif Abu Median, A. et al. Clinical trial of E1B-deleted adenovirus (dl1520) gene therapy for hepatocellular carcinoma. Cancer Gene Ther 9, 254–259 (2002). https://doi.org/10.1038/sj.cgt.7700431

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