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

doi:10.1080/2162402x.2017.1408749

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

38 Citations (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.

Original language	English
Article number	e1408749
Journal	OncoImmunology
Volume	7
Issue number	3
Number of pages	12
ISSN	2162-4011
DOIs	https://doi.org/10.1080/2162402x.2017.1408749
Publication status	Published - 4 Mar 2018

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Palladini, A., Thrane, S., Janitzek, C. M., Pihl, J., Clemmensen, S. B., de Jongh, W. A., Clausen, T. M., Nicoletti, G., Landuzzi, L., Penichet, M. L., Balboni, T., Ianzano, M. L., Giusti, V., Theander, T. G., Nielsen, M. A., Salanti, A., Lollini, P-L., Nanni, P., & Sander, A. F. (2018). Virus-like particle display of HER2 induces potent anti-cancer responses. OncoImmunology, 7(3), [e1408749]. https://doi.org/10.1080/2162402x.2017.1408749

Palladini, A, Thrane, S , Janitzek, CM , Pihl, J , Clemmensen, SB, de Jongh, WA, Clausen, TM, Nicoletti, G, Landuzzi, L, Penichet, ML, Balboni, T, Ianzano, ML, Giusti, V, Theander, TG , Nielsen, MA , Salanti, A, Lollini, P-L, Nanni, P & Sander, AF 2018, 'Virus-like particle display of HER2 induces potent anti-cancer responses', OncoImmunology, vol. 7, no. 3, e1408749. https://doi.org/10.1080/2162402x.2017.1408749

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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.",

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AU - Giusti, Veronica

AU - Theander, Thor G

AU - Nielsen, Morten A

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AB - 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.

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

Abstract

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