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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1-13
Number of pages13
JournalOncoImmunology
Volume7
Issue number3
DOIs
Publication statusPublished - Mar 4 2018

Keywords

  • breast cancer
  • HER2
  • nano-particle
  • Therapeutic vaccination
  • vaccine
  • virus-like particle

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology

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