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Virus-like particle display of HER2 induces potent anti-cancer responses

  • Arianna Palladini
  • , Susan Thrane
  • , Christoph M Janitzek
  • , Jessica Pihl
  • , Stine B Clemmensen
  • , Willem Adriaan de Jongh
  • , Thomas M Clausen
  • , Giordano Nicoletti
  • , Lorena Landuzzi
  • , Manuel L Penichet
  • , Tania Balboni
  • , Marianna L Ianzano
  • , Veronica Giusti
  • , Thor G Theander
  • , Morten A Nielsen
  • , Ali Salanti
  • , Pier-Luigi Lollini
  • , Patrizia Nanni
  • , Adam F Sander
    103 Citationer (Scopus)

    Abstract

    Overexpression of human epidermal growth factor receptor-2 (HER2) occurs in 20-30% of invasive breast cancers. Monoclonal antibody therapy is effective in treating HER2-driven mammary carcinomas, but its utility is limited by high costs, side effects and development of resistance. Active vaccination may represent a safer, more effective and cheaper alternative, although the induction of strong and durable autoantibody responses is hampered by immune-tolerogenic mechanisms. Using a novel virus-like particle (VLP) based vaccine platform we show that directional, high-density display of human HER2 on the surface of VLPs, allows induction of therapeutically potent anti-HER2 autoantibody responses. Prophylactic vaccination reduced spontaneous development of mammary carcinomas by 50%-100% in human HER2 transgenic mice and inhibited the growth of HER2-positive tumors implanted in wild-type mice. The HER2-VLP vaccine shows promise as a new cost-effective modality for prevention and treatment of HER2-positive cancer. The VLP platform may represent an effective tool for development of vaccines against other non-communicable diseases.

    OriginalsprogEngelsk
    TidsskriftOncoImmunology
    Vol/bind7
    Udgave nummer3
    Sider (fra-til)e1408749
    ISSN2162-4011
    DOI
    StatusUdgivet - 2018

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