E1B-deleted Adenovirus (dl1520) Gene Therapy for Patients With Primary and Secondary Liver Tumors

Hum Gene Ther. 2001 Feb 10;12(3):219-26. doi: 10.1089/10430340150218369.

Abstract

Clinical studies were performed with a recombinant mutant adenovirus with an E1B 55-kDa deletion, dl1520, to assess its toxicity and efficacy in patients with irresectable primary and secondary liver tumors. A phase I study showed that dl1520 was well tolerated when administered directly intratumorally, intraarterially, or intravenously up to a dose of 3 x 10(11) PFU. Ultrastructural examination of tissue showed the presence of adenovirus in cell cytoplasm around the nucleus and revealed two dissimilar end points of cell death after virus infection: a preapoptotic sequence and necrosis. A phase II study showed that the combination of dl1520 and 5-fluorouracil (5-FU), when infused into the hepatic artery, was well tolerated. Further improvement in the recombinant vector design will be needed in order to achieve better clinical response.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics*
  • Adenovirus E1B Proteins / genetics*
  • Adult
  • Aged
  • Aged, 80 and over
  • Antimetabolites, Antineoplastic / therapeutic use
  • Apoptosis
  • Carcinoma, Hepatocellular / therapy
  • Carcinoma, Hepatocellular / ultrastructure
  • Cell Nucleus / metabolism
  • Chromatin / ultrastructure
  • Combined Modality Therapy
  • Cytoplasm / metabolism
  • Female
  • Fluorouracil / therapeutic use
  • Gene Deletion
  • Genetic Therapy / methods*
  • Humans
  • Liver Neoplasms / pathology*
  • Liver Neoplasms / secondary*
  • Liver Neoplasms / therapy*
  • Male
  • Microscopy, Electron
  • Middle Aged
  • Necrosis
  • Neoplasm Metastasis

Substances

  • Adenovirus E1B Proteins
  • Antimetabolites, Antineoplastic
  • Chromatin
  • Fluorouracil