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

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...

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Detalles Bibliográficos
Autores principales: Palladini, Arianna, Thrane, Susan, Janitzek, Christoph M., Pihl, Jessica, Clemmensen, Stine B., de Jongh, Willem Adriaan, Clausen, Thomas M., Nicoletti, Giordano, Landuzzi, Lorena, Penichet, Manuel L., Balboni, Tania, Ianzano, Marianna L., Giusti, Veronica, Theander, Thor G., Nielsen, Morten A., Salanti, Ali, Lollini, Pier-Luigi, Nanni, Patrizia, Sander, Adam F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5790387/
https://www.ncbi.nlm.nih.gov/pubmed/29399414
http://dx.doi.org/10.1080/2162402X.2017.1408749
Descripción
Sumario: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.