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

TY - JOUR

T1 - Virus-like particle display of HER2 induces potent anti-cancer responses

AU - Palladini, Arianna

AU - Thrane, Susan

AU - Janitzek, Christoph M

AU - Pihl, Jessica

AU - Clemmensen, Stine B

AU - de Jongh, Willem Adriaan

AU - Clausen, Thomas M

AU - Nicoletti, Giordano

AU - Landuzzi, Lorena

AU - Penichet, Manuel L

AU - Balboni, Tania

AU - Ianzano, Marianna L

AU - Giusti, Veronica

AU - Theander, Thor G

AU - Nielsen, Morten A

AU - Salanti, Ali

AU - Lollini, Pier-Luigi

AU - Nanni, Patrizia

AU - Sander, Adam F

PY - 2018/3/4

Y1 - 2018/3/4

N2 - 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.

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.

U2 - 10.1080/2162402x.2017.1408749

DO - 10.1080/2162402x.2017.1408749

M3 - Journal article

C2 - 29399414

SN - 2162-4011

VL - 7

JO - OncoImmunology

JF - OncoImmunology

IS - 3

M1 - e1408749

ER -