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

Oncoimmunology. 2018 Jan 5;7(3):e1408749. doi: 10.1080/2162402X.2017.1408749. eCollection 2018.

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.

Keywords: HER2; Therapeutic vaccination; breast cancer; nano-particle; vaccine; virus-like particle.

Publication types

  • Research Support, Non-U.S. Gov't

Grants and funding

This work was supported by grants from the Danish Research Councils, The Eurostars program and the European Research councils (ERC). This work was also supported by a grant to P-L Lollini (pier.lollini@unibo.it) from the Italian Association for Cancer Research (AIRC), IG15324. The authors would like to thank Jens Hedelund Madsen for technical assistance.