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Novel gene therapy strategy to accomplish growth factor modulation induces enhanced tumor cell chemosensitivity

M N Barnes1, J S Deshane, G P Siegal

  • 1Departments of Obstetrics and Gynecology and Pathology, Cell Biology, and Surgery, and Gene Therapy Program, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|July 1, 1996
PubMed

Insights

Gene therapy targeting erbB-2 (a cell surface protein) can overcome tumor cell chemoresistance. Down-regulating erbB-2 expression enhances sensitivity to chemotherapy drugs like cisplatin.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gene Therapy

Background:

  • Overexpression of the cell surface glycoprotein erbB-2 is linked to intrinsic tumor cell chemoresistance.
  • Strategies to down-regulate erbB-2 expression have shown potential in enhancing tumor cell chemosensitivity.

Purpose of the Study:

  • To investigate a novel gene therapy approach using an intracellular single chain antibody to down-modulate erbB-2 expression.
  • To demonstrate enhanced chemosensitivity in erbB-2 overexpressing tumor cells and stable clones.

Main Methods:

  • Utilized a plasmid construct encoding an intracellular single chain antibody targeting erbB-2.
  • Tested the chemosensitivity of erbB-2 overexpressing tumor cells and stable clones to cisplatin.

Main Results:

  • Demonstrated enhanced chemosensitivity to cisplatin in tumor cells with down-regulated erbB-2 expression.
  • Confirmed the role of erbB-2 in mediating tumor cell chemoresistance through experimental models.

Conclusions:

  • The intracellular single chain antibody gene therapy approach effectively overcomes erbB-2-mediated tumor cell chemoresistance.
  • This novel gene therapy strategy offers a promising method to enhance the efficacy of chemotherapy in erbB-2-overexpressing tumors.

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