Gene therapy with apoptin induces regression of xenografted human hepatomas.
The chicken anemia virus-derived Apoptin protein shows remarkable specificity; namely, it induces apoptosis in tumor cells, but not in normal diploid cells. We have exploited the Apoptin gene for use in cancer gene therapy. Here we demonstrate that adenovirus-mediated intratumoral transfer and expression of the Apoptin gene results in regression or complete remission of human hepatomas grown as xenografts in immune-deficient mice, and significantly increases their survival long term. Early after intratumoral injection, Apoptin could be detected in significant quantities by Western blot analyses and immunohistochemistry. Furthermore, cell death and disruption of the tumor integrity were apparent in the transduced regions. This experimental gene therapeutic strategy constitutes a unique example of specific antitumor activity using a virus-derived gene with broad-spectrum applicability.
van der Eb
Marjolijn M
MM
Department of Molecular Cell Biology, Leiden University Medical Centre, The Netherlands.
Pietersen
Alexandra M
AM
Speetjens
Frank M
FM
Kuppen
Peter J K
PJ
van de Velde
Cornelis J H
CJ
Noteborn
Mathieu H M
MH
Hoeben
Rob C
RC
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D001973:Bromodeoxyuridine; D002213:Capsid / Q000235:genetics* / Q000378:metabolism; D036022:Capsid Proteins; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000628:therapy*; D002455:Cell Division / Q000502:physiology; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000235:genetics; D006801:Humans; D015552:Injections, Intralesional; D007763:Lac Operon / Q000502:physiology; D008114:Liver Neoplasms, Experimental / Q000473:pathology / Q000628:therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D015996:Survival Rate; D006377:T-Lymphocytes, Helper-Inducer / Q000378:metabolism; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D036022:Capsid Proteins; C091717:VP3 protein, Chicken anemia virus; D001973:Bromodeoxyuridine