A slowly growing human cholangiocarcinoma is highly sensitive to HSVtk gene therapy

Michaela S. Banck, Peter Meier-Abt, Thomas Gerloff, Silvio Hemmi, Andrea S. Beutler

Research output: Contribution to journalArticle

Abstract

Background Cholangiocarcinoma treatment may be improved by local delivery of suicide gene therapy. Herpes simplex virus thymidine kinase (HSVtk) gene delivery followed by ganciclovir is a well established approach but its efficacy in slowly growing tumors is uncertain and its use against cholangiocarcinoma has not been studied. Methods The human bile duct carcinoma cell line Sk-Cha-1 was used as a tumor model. Retroviral vectors were used for gene transfer in vitro. Adenoviral vectors were used for gene transfer in vitro and for gene transfer into established subcutaneous tumors in nude mice in vivo. Results HSVtk-transduced SK-ChA-1 cells were highly sensitive towards ganciclovir in vitro (LD50=0.02 μmol/l), were susceptible to bystander killing, and were easily infectable by adenovirus (90% at a multiplicity of infection of 100). Sk-Cha-1 tumors expressing HSVtk could be eradicated in vivo by ganciclovir administration while control tumors grew progressively until animals became symptomatic at 4 1/2 months. Adenovirus mediated HSVtk gene therapy of established tumors in vivo demonstrated a 90% reduction of tumor size. Conclusion A slowly growing human cholangiocarcinoma was highly susceptible to adenovirus mediated HSVtk/ganciclovir gene therapy. Local gene therapy delivery may be adapted for use by ERCP for palliation of this malignancy.

Original languageEnglish (US)
Pages (from-to)343-353
Number of pages11
JournalGI Cancer
Volume3
Issue number5
StatePublished - Dec 1 2001

Keywords

  • Adenovirus
  • Cholangiocarcinoma
  • Gene therapy
  • Herpes simplex thymidine kinase

ASJC Scopus subject areas

  • Oncology
  • Gastroenterology

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    Banck, M. S., Meier-Abt, P., Gerloff, T., Hemmi, S., & Beutler, A. S. (2001). A slowly growing human cholangiocarcinoma is highly sensitive to HSVtk gene therapy. GI Cancer, 3(5), 343-353.