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HER2-Targeted Polyinosine/Polycytosine Therapy Inhibits Tumor Growth and Modulates the Tumor Immune Microenvironment

Maya Zigler1, Alexei Shir1, Salim Joubran1

  • 1Unit of Cellular Signaling, Department of Biological Chemistry, The Hebrew University of Jerusalem, Jerusalem, Israel.

Cancer Immunology Research
|June 1, 2016
PubMed

Insights

A novel HER2-homing polyinosine/polycytosine (pIC) chemical vector effectively eliminates HER2-positive breast cancer cells, including resistant types. This targeted therapy stimulates antitumor immunity and inhibits tumor growth in mice.

Area of Science:

  • Oncology
  • Immunology
  • Nanotechnology

Background:

  • Targeted therapies for HER2-positive breast cancer are needed, as current treatments face resistance.
  • HER2 overexpression occurs in about 20% of breast cancer patients.
  • HER2 is not essential for survival in all targeted cancer cells, leading to treatment failure.

Purpose of the Study:

  • To develop and evaluate a novel HER2-homing chemical vector for treating HER2-positive breast cancer.
  • To investigate the mechanisms of action and antitumor effects of the targeted vector.

Main Methods:

  • Development of a polyinosine/polycytosine (pIC) chemical vector targeted to HER2.
  • In vitro testing on HER2-overexpressing breast cancer cells, including trastuzumab-resistant lines.
  • In vivo studies in immunocompetent mice bearing HER2-overexpressing tumors.

Main Results:

  • The HER2-targeted pIC vector induced cell death in HER2-overexpressing breast cancer cells, overcoming trastuzumab resistance.
  • Targeting pIC to tumors activated multiple cell-killing mechanisms and bystander effects, including type I IFN induction and immune cell recruitment.
  • HER2-targeted pIC significantly inhibited tumor growth in immunocompetent mice.

Conclusions:

  • A HER2-homing pIC vector shows potent antitumor activity against HER2-positive breast cancer.
  • This targeted approach stimulates antitumor immunity, offering a promising new therapeutic strategy.
  • The findings suggest new avenues for treating HER2-positive breast cancer, particularly resistant forms.

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