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E1B-deleted adenovirus (dl1520) gene therapy for patients with primary and secondary liver tumors

N A Habib1, C E Sarraf, R R Mitry

  • 1Department of Surgery, Imperial College School of Medicine, Hammersmith Hospital, London, W12 0NN, UK. Nagy.Habib@ic.ac.uk

Human Gene Therapy
|February 15, 2001
PubMed

Insights

This study evaluated a modified adenovirus (dl1520) for liver cancer treatment. While dl1520 showed good tolerance and induced cell death, further vector improvements are needed for better clinical outcomes in patients.

Area of Science:

  • Oncolytic virotherapy
  • Gene therapy
  • Hepatocellular carcinoma research

Background:

  • Recombinant mutant adenovirus dl1520 targets liver tumors.
  • Previous studies assessed adenovirus toxicity and efficacy.

Purpose of the Study:

  • Evaluate the safety and effectiveness of dl1520 in patients with liver tumors.
  • Assess the combination therapy of dl1520 and 5-fluorouracil (5-FU).

Main Methods:

  • Phase I and II clinical trials.
  • Intratumoral, intra-arterial, and intravenous administration of dl1520.
  • Combination therapy with 5-FU via hepatic artery infusion.

Main Results:

  • dl1520 was well tolerated at doses up to 3 x 10(11) PFU via multiple administration routes.
  • Adenovirus presence and two cell death pathways (preapoptosis, necrosis) observed.
  • Combination of dl1520 and 5-FU was well tolerated.

Conclusions:

  • Recombinant adenovirus dl1520 demonstrates safety in liver cancer patients.
  • Further optimization of adenovirus vectors is necessary for enhanced clinical efficacy.

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