Persistent expression of biologically active anti-HER2 antibody by AAVrh.10-mediated gene transfer

G. Wang, J. Qiu, R. Wang, A. Krause, J. L. Boyer, N. R. Hackett, Ronald Crystal

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Trastuzumab (Herceptin) is a recombinant humanized monoclonal antibody (mAb) directed against an extracellular region of the human epidermal growth-factor receptor type 2 (HER2) protein. We hypothesized that a single adeno-associated virus (AAV)-mediated genetic delivery of an anti-HER2 antibody should be effective in mediating long-term production of anti-HER2 and in suppressing the growth of human tumors in a xenograft model in nude mice. The adeno-associated virus gene transfer vector AAVrh.10αHER2 was constructed based on a non-human primate AAV serotype rh.10 to express the complementary DNAs for the heavy and light chains of mAb 4D5, the murine precursor to trastuzumab. The data show that genetically transferred anti-HER2 selectively bound human HER2 protein and suppressed the proliferation of HER2+ tumor cell lines. A single administration of AAVrh.10αHER2 provided long-term therapeutic levels of anti-HER2 antibody expression without inducing an anti-idiotype response, suppressed the growth of HER2 tumors and increased the survival of tumor bearing mice. In the context that trastuzumab therapy requires frequent and repeated administration, this strategy might be developed as an alternate platform for delivery of anti-HER2 therapy.

Original languageEnglish
Pages (from-to)559-570
Number of pages12
JournalCancer Gene Therapy
Volume17
Issue number8
DOIs
Publication statusPublished - 1 Aug 2010
Externally publishedYes

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Keywords

  • Adeno-associated virus
  • Breast cancer
  • Gene delivery
  • Herceptin
  • Trastuzumab

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Cancer Research

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