Gene therapy for breast and ovarian cancer with BRCA1

David L. Tait, Roy A. Jensen, Jeffrey T. Holt, David H. Johnson, Julie Gralow, Mary Claire King

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

As an initial step toward gene therapy for ovarian cancer, we conducted a Phase 1 trial to assess the pharmacokinetics and toxicity of intraperitoneal BRCA1sv retroviral vector therapy. Gene transfer and expression were documented by PCR, southern blot, RT-PCR and nuclease protection assays. Pharmacokinetics were assessed by PCR and southern blots detecting vector DNA, and toxicity was evaluated by clinical exam and fluid analysis. Three of twelve patients developed an acute sterile peritonitis which spontaneously resolved within 48 hours. Plasma and peritoneal antibodies to the retroviral envelope protein were detected only in patients treated with the highest dose levels but not in others, despite repeat dosing for an interval of up to four months. Eight patients showed stable disease for 4 to 16 weeks. Three patients showed tumor reduction with diminished miliary tumor implants at reoperation (two patients) and radiographic shrinkage of measurable disease (one patient). Ovarian cancer may provide an imporant model for retroviral gene therapy studies due to vector stability, minimal antibody response, and access to tumor by intraperitoneal therapy.

Original languageEnglish (US)
Pages (from-to)89-98
Number of pages10
JournalBreast Disease
Volume10
Issue number1-2
DOIs
StatePublished - Apr 1998

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Tait, D. L., Jensen, R. A., Holt, J. T., Johnson, D. H., Gralow, J., & King, M. C. (1998). Gene therapy for breast and ovarian cancer with BRCA1. Breast Disease, 10(1-2), 89-98. https://doi.org/10.3233/BD-1998-101-211