title: E1B-deleted adenovirus (dl1520) gene therapy for patients with primary and secondary liver tumors.
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.
authors.affiliation: Department of Surgery, Imperial College School of Medicine, Hammersmith Hospital, London, W12 0NN, UK. Nagy.Habib@ic.ac.uk
authors.forename: N A
authors.initials: NA
authors.lastname: Habib
authors.forename: C E
authors.initials: CE
authors.lastname: Sarraf
authors.forename: R R
authors.initials: RR
authors.lastname: Mitry
authors.forename: R
authors.initials: R
authors.lastname: Havlík
authors.forename: J
authors.initials: J
authors.lastname: Nicholls
authors.forename: M
authors.initials: M
authors.lastname: Kelly
authors.forename: C C
authors.initials: CC
authors.lastname: Vernon
authors.forename: D
authors.initials: D
authors.lastname: Gueret-Wardle
authors.forename: R
authors.initials: R
authors.lastname: El-Masry
authors.forename: H
authors.initials: H
authors.lastname: Salama
authors.forename: R
authors.initials: R
authors.lastname: Ahmed
authors.forename: N
authors.initials: N
authors.lastname: Michail
authors.forename: E
authors.initials: E
authors.lastname: Edward
authors.forename: S L
authors.initials: SL
authors.lastname: Jensen
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D017501:Adenovirus E1B Proteins / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000628:therapy / Q000648:ultrastructure; D002467:Cell Nucleus / Q000378:metabolism; D002843:Chromatin / Q000648:ultrastructure; D003131:Combined Modality Therapy; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D017353:Gene Deletion; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology* / Q000556:secondary* / Q000628:therapy*; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D009336:Necrosis; D009362:Neoplasm Metastasis
chemical_list: D017501:Adenovirus E1B Proteins; D000964:Antimetabolites, Antineoplastic; D002843:Chromatin; D005472:Fluorouracil