Overexpression of human epidermal growth factor receptor-2 (HER2) occurs in 20â30% 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.
Palladini, A., Thrane, S., Janitzek, C.M., Pihl, J., Clemmensen, S.B., de Jongh, W.A., et al. (2018). Virus-like particle display of HER2 induces potent anti-cancer responses. ONCOIMMUNOLOGY, 7(3), 1-12 [10.1080/2162402X.2017.1408749].
Virus-like particle display of HER2 induces potent anti-cancer responses
Palladini, Arianna;Nicoletti, Giordano;Landuzzi, Lorena;Balboni, Tania;Ianzano, Marianna L.;Giusti, Veronica;Lollini, Pier-Luigi;Nanni, Patrizia;
2018
Abstract
Overexpression of human epidermal growth factor receptor-2 (HER2) occurs in 20â30% 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.File | Dimensione | Formato | |
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HER2-VLP OncoImmunology.pdf
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