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HER2-targeted gene transfer

B J Foster1, J A Kern

  • 1University of Iowa College of Medicine, Department of Internal Medicine, Iowa City 52242, USA.

Human Gene Therapy
|April 10, 1997
PubMed
Summary
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Targeting human epidermal growth factor receptor-2 (HER2) with antibody-DNA complexes facilitates selective gene transfer into HER2-expressing cancer cells. This approach shows promise for targeted gene therapy delivery.

Area of Science:

  • Biotechnology
  • Molecular Biology
  • Cancer Research

Background:

  • Selective gene transfer to specific cells is a major challenge in somatic gene therapy.
  • The human epidermal growth factor receptor-2 (HER2), highly expressed in many epithelial tumors, presents a potential target for gene delivery.

Purpose of the Study:

  • To investigate the potential of HER2 as an immunological target for gene transfer.
  • To develop and test antibody-DNA complexes for HER2-targeted gene delivery.

Main Methods:

  • Constructed complexes of a luciferase expression vector (pRSVLuc) with a HER2 antibody (rhuMAbHER2) modified with poly-L-lysine (PL).
  • Tested gene transfer efficiency in HER2-expressing (NIH3T3.HER2, BT474, SKBR3) and non-expressing (NIH3T3) cell lines in vitro.
  • Assessed specificity by preincubating cells with unconjugated HER2 antibody.

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Main Results:

  • HER2-targeted complexes achieved 180-fold higher luciferase expression in HER2-expressing cells compared to irrelevant antibody conjugates.
  • Successful gene transfer and expression were observed in HER2-positive adenocarcinoma cell lines (BT474, SKBR3).
  • Specificity was confirmed as preincubation with unconjugated HER2 antibody reduced gene transfer by 95%.

Conclusions:

  • HER2 is a viable target for selective gene transfer strategies.
  • Poly-L-lysine-HER2 antibody-DNA complexes are effective vehicles for directing gene transfer to HER2-expressing cells.
  • This targeted approach holds potential for advancing somatic gene therapy applications.