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

Research output: Contribution to journalArticle

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 languageEnglish
Pages (from-to)1-13
Number of pages13
JournalOncoImmunology
Volume7
Issue number3
DOIs
Publication statusPublished - Mar 4 2018

Fingerprint

Virion
Neoplasms
Virus-Like Particle Vaccines
Breast Neoplasms
Autoantibodies
Vaccination
Costs and Cost Analysis
human ERBB2 protein
Transgenic Mice
Vaccines
Monoclonal Antibodies
Therapeutics
Growth

Keywords

  • breast cancer
  • HER2
  • nano-particle
  • Therapeutic vaccination
  • vaccine
  • virus-like particle

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Oncology

Cite this

Palladini, A., Thrane, S., Janitzek, C. M., Pihl, J., Clemmensen, S. B., de Jongh, W. A., ... Sander, A. F. (2018). Virus-like particle display of HER2 induces potent anti-cancer responses. OncoImmunology, 7(3), 1-13. https://doi.org/10.1080/2162402X.2017.1408749

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

In: OncoImmunology, Vol. 7, No. 3, 04.03.2018, p. 1-13.

Research output: Contribution to journalArticle

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, PL, Nanni, P & Sander, AF 2018, 'Virus-like particle display of HER2 induces potent anti-cancer responses', OncoImmunology, vol. 7, no. 3, pp. 1-13. https://doi.org/10.1080/2162402X.2017.1408749
Palladini A, Thrane S, Janitzek CM, Pihl J, Clemmensen SB, de Jongh WA et al. Virus-like particle display of HER2 induces potent anti-cancer responses. OncoImmunology. 2018 Mar 4;7(3):1-13. https://doi.org/10.1080/2162402X.2017.1408749
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. / Virus-like particle display of HER2 induces potent anti-cancer responses. In: OncoImmunology. 2018 ; Vol. 7, No. 3. pp. 1-13.
@article{4c34610986d1448f9b016867cf9ee65d,
title = "Virus-like particle display of HER2 induces potent anti-cancer responses",
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 = "breast cancer, HER2, nano-particle, Therapeutic vaccination, vaccine, virus-like particle",
author = "Arianna Palladini and Susan Thrane and Janitzek, {Christoph M.} and Jessica Pihl and Clemmensen, {Stine B.} and {de Jongh}, {Willem Adriaan} and Clausen, {Thomas M.} and Giordano Nicoletti and Lorena Landuzzi and Penichet, {Manuel L.} and Tania Balboni and Ianzano, {Marianna L.} and Veronica Giusti and Theander, {Thor G.} and Nielsen, {Morten A.} and Ali Salanti and Lollini, {Pier Luigi} and Patrizia Nanni and Sander, {Adam F.}",
year = "2018",
month = "3",
day = "4",
doi = "10.1080/2162402X.2017.1408749",
language = "English",
volume = "7",
pages = "1--13",
journal = "OncoImmunology",
issn = "2162-4011",
publisher = "Taylor and Francis Inc.",
number = "3",

}

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.

KW - breast cancer

KW - HER2

KW - nano-particle

KW - Therapeutic vaccination

KW - vaccine

KW - virus-like particle

UR - http://www.scopus.com/inward/record.url?scp=85041106221&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85041106221&partnerID=8YFLogxK

U2 - 10.1080/2162402X.2017.1408749

DO - 10.1080/2162402X.2017.1408749

M3 - Article

AN - SCOPUS:85041106221

VL - 7

SP - 1

EP - 13

JO - OncoImmunology

JF - OncoImmunology

SN - 2162-4011

IS - 3

ER -