An HER2-displaying virus-like particle vaccine protects from challenge with mammary carcinoma cells in a mouse model

Lisa Nika, Sara Cuadrado-Castano, Guha Asthagiri Arunkumar, Clemens Grünwald-Gruber, Meagan McMahon, Krisztina Koczka, Adolfo García-Sastre, Florian Krammer, Reingard Grabherr

Research output: Contribution to journalArticle

Abstract

Human epidermal growth factor receptor-2 (HER2) is upregulated in 20% to 30% of breast cancers and is a marker of a poor outcome. Due to the development of resistance to passive immunotherapy with Trastuzumab, active anti-HER2 vaccination strategies that could potentially trigger durable tumor-specific immune responses have become an attractive research area. Recently, we have shown that budded virus-like particles (VLPs) produced in Sf9 insect cells are an ideal platform for the expression of complex membrane proteins. To assess the efficacy of antigendisplaying VLPs as active cancer vaccines, BALB/c mice were immunized with insect cell glycosylated and mammalian-like glycosylated HER2-displaying VLPs in combination with two different adjuvants and were challenged with HER2-positive tumors. Higher HER2-specific antibody titers and effector functions were induced in mice vaccinated with insect cell glycosylated HER2 VLPs compared to mammalian-like glycosylated counterparts. Moreover, insect cell glycosylated HER2 VLPs elicited a protective effect in mice grafted with HER2-positive mammary carcinoma cells. Interestingly, no protection was observed in mice that were adjuvanted with Poly (I:C). Here, we show that antigendisplaying VLPs produced in Sf9 insect cells were able to induce robust and durable immune responses in vivo and have the potential to be utilized as active cancer vaccines.

Original languageEnglish
Article number41
JournalVaccines
Volume7
Issue number2
DOIs
Publication statusPublished - 01-06-2019

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Virus-Like Particle Vaccines
Virion
Breast Neoplasms
Insects
Sf9 Cells
Cancer Vaccines
Passive Immunization
human ERBB2 protein
Neoplasms
Membrane Proteins
Vaccination

All Science Journal Classification (ASJC) codes

  • Immunology
  • Pharmacology
  • Drug Discovery
  • Infectious Diseases
  • Pharmacology (medical)

Cite this

Nika, Lisa ; Cuadrado-Castano, Sara ; Arunkumar, Guha Asthagiri ; Grünwald-Gruber, Clemens ; McMahon, Meagan ; Koczka, Krisztina ; García-Sastre, Adolfo ; Krammer, Florian ; Grabherr, Reingard. / An HER2-displaying virus-like particle vaccine protects from challenge with mammary carcinoma cells in a mouse model. In: Vaccines. 2019 ; Vol. 7, No. 2.
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abstract = "Human epidermal growth factor receptor-2 (HER2) is upregulated in 20{\%} to 30{\%} of breast cancers and is a marker of a poor outcome. Due to the development of resistance to passive immunotherapy with Trastuzumab, active anti-HER2 vaccination strategies that could potentially trigger durable tumor-specific immune responses have become an attractive research area. Recently, we have shown that budded virus-like particles (VLPs) produced in Sf9 insect cells are an ideal platform for the expression of complex membrane proteins. To assess the efficacy of antigendisplaying VLPs as active cancer vaccines, BALB/c mice were immunized with insect cell glycosylated and mammalian-like glycosylated HER2-displaying VLPs in combination with two different adjuvants and were challenged with HER2-positive tumors. Higher HER2-specific antibody titers and effector functions were induced in mice vaccinated with insect cell glycosylated HER2 VLPs compared to mammalian-like glycosylated counterparts. Moreover, insect cell glycosylated HER2 VLPs elicited a protective effect in mice grafted with HER2-positive mammary carcinoma cells. Interestingly, no protection was observed in mice that were adjuvanted with Poly (I:C). Here, we show that antigendisplaying VLPs produced in Sf9 insect cells were able to induce robust and durable immune responses in vivo and have the potential to be utilized as active cancer vaccines.",
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Nika, L, Cuadrado-Castano, S, Arunkumar, GA, Grünwald-Gruber, C, McMahon, M, Koczka, K, García-Sastre, A, Krammer, F & Grabherr, R 2019, 'An HER2-displaying virus-like particle vaccine protects from challenge with mammary carcinoma cells in a mouse model', Vaccines, vol. 7, no. 2, 41. https://doi.org/10.3390/vaccines7020041

An HER2-displaying virus-like particle vaccine protects from challenge with mammary carcinoma cells in a mouse model. / Nika, Lisa; Cuadrado-Castano, Sara; Arunkumar, Guha Asthagiri; Grünwald-Gruber, Clemens; McMahon, Meagan; Koczka, Krisztina; García-Sastre, Adolfo; Krammer, Florian; Grabherr, Reingard.

In: Vaccines, Vol. 7, No. 2, 41, 01.06.2019.

Research output: Contribution to journalArticle

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AU - Grabherr, Reingard

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