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Updated: Oct 2, 2026
High-Efficiency Transduction of Liver Cancer Cells by Recombinant Adeno-Associated Virus Serotype 3 Vectors
Published on: March 22, 2011
Clinical trial of E1B-deleted adenovirus (dl1520) gene therapy for hepatocellular carcinoma
Nagy Habib1, Hosny Salama, Ahmed Abd El Latif Abu Median
1Division of Surgery, Anaesthetics and Intensive Care, Imperial College School of Medicine, Hammersmith Hospital Campus, London W12 ONN, UK. nagy.habib@ic.ac.uk
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.
Insights
Gene therapy using dl1520 adenovirus showed minimal toxicity for hepatocellular carcinoma (HCC) patients. However, this hepatocellular carcinoma treatment did not demonstrate significant tumor control, suggesting a need for improved gene therapy vectors.
Area of Science:
- Hepatocellular Carcinoma Research
- Gene Therapy
- Oncology
Background:
- Hepatocellular carcinoma (HCC) is a prevalent cancer with poor prognosis and limited effective therapies.
- Tumor suppressor gene inactivation, particularly p53, is common in HCC.
- Gene therapy offers a potential strategy for tumor growth control in p53-mutated cancers.
Purpose of the Study:
- To evaluate the safety and efficacy of E1B-deleted adenovirus (dl1520) gene therapy in HCC patients.
- To compare dl1520 gene therapy with percutaneous ethanol injection for HCC treatment.
Main Methods:
- An open-label, randomized prospective study involving ten HCC patients with posthepatitis cirrhosis.
- Patients were randomized to receive either dl1520 gene therapy or percutaneous ethanol injection.
- Toxicity, complications, and treatment response were monitored.
Main Results:
- dl1520 gene therapy was well-tolerated with minimal toxicity (Grade I-II fever, stable performance status).
- One partial response and four progressive diseases were observed in the dl1520 group.
- The control group showed two stable diseases and three progressive diseases.
Conclusions:
- E1B-deleted adenovirus (dl1520) is safe for HCC patients but did not provide significant tumor control.
- Further research is needed to develop more effective gene therapy vectors for clinical impact in HCC treatment.
