E1B-deleted adenovirus (dl1520) gene therapy for patients with primary and secondary liver tumors.
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.
Habib
N A
NA
Department of Surgery, Imperial College School of Medicine, Hammersmith Hospital, London, W12 0NN, UK. Nagy.Habib@ic.ac.uk
Sarraf
C E
CE
Mitry
R R
RR
Havlík
R
R
Nicholls
J
J
Kelly
M
M
Vernon
C C
CC
Gueret-Wardle
D
D
El-Masry
R
R
Salama
H
H
Ahmed
R
R
Michail
N
N
Edward
E
E
Jensen
S L
SL
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
D017501:Adenovirus E1B Proteins; D000964:Antimetabolites, Antineoplastic; D002843:Chromatin; D005472:Fluorouracil