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A HER2-Displaying Virus-Like Particle Vaccine Protects from Challenge with Mammary Carcinoma Cells in a Mouse Model
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-speci...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6631560/ https://www.ncbi.nlm.nih.gov/pubmed/31137559 http://dx.doi.org/10.3390/vaccines7020041 |
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author | Nika, Lisa Cuadrado-Castano, Sara Asthagiri Arunkumar, Guha Grünwald-Gruber, Clemens McMahon, Meagan Koczka, Krisztina García-Sastre, Adolfo Krammer, Florian Grabherr, Reingard |
author_facet | Nika, Lisa Cuadrado-Castano, Sara Asthagiri Arunkumar, Guha Grünwald-Gruber, Clemens McMahon, Meagan Koczka, Krisztina García-Sastre, Adolfo Krammer, Florian Grabherr, Reingard |
author_sort | Nika, Lisa |
collection | PubMed |
description | 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 antigen-displaying 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 antigen-displaying 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. |
format | Online Article Text |
id | pubmed-6631560 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-66315602019-08-19 A HER2-Displaying Virus-Like Particle Vaccine Protects from Challenge with Mammary Carcinoma Cells in a Mouse Model Nika, Lisa Cuadrado-Castano, Sara Asthagiri Arunkumar, Guha Grünwald-Gruber, Clemens McMahon, Meagan Koczka, Krisztina García-Sastre, Adolfo Krammer, Florian Grabherr, Reingard Vaccines (Basel) Article 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 antigen-displaying 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 antigen-displaying 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. MDPI 2019-05-20 /pmc/articles/PMC6631560/ /pubmed/31137559 http://dx.doi.org/10.3390/vaccines7020041 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Nika, Lisa Cuadrado-Castano, Sara Asthagiri Arunkumar, Guha Grünwald-Gruber, Clemens McMahon, Meagan Koczka, Krisztina García-Sastre, Adolfo Krammer, Florian Grabherr, Reingard A HER2-Displaying Virus-Like Particle Vaccine Protects from Challenge with Mammary Carcinoma Cells in a Mouse Model |
title | A HER2-Displaying Virus-Like Particle Vaccine Protects from Challenge with Mammary Carcinoma Cells in a Mouse Model |
title_full | A HER2-Displaying Virus-Like Particle Vaccine Protects from Challenge with Mammary Carcinoma Cells in a Mouse Model |
title_fullStr | A HER2-Displaying Virus-Like Particle Vaccine Protects from Challenge with Mammary Carcinoma Cells in a Mouse Model |
title_full_unstemmed | A HER2-Displaying Virus-Like Particle Vaccine Protects from Challenge with Mammary Carcinoma Cells in a Mouse Model |
title_short | A HER2-Displaying Virus-Like Particle Vaccine Protects from Challenge with Mammary Carcinoma Cells in a Mouse Model |
title_sort | her2-displaying virus-like particle vaccine protects from challenge with mammary carcinoma cells in a mouse model |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6631560/ https://www.ncbi.nlm.nih.gov/pubmed/31137559 http://dx.doi.org/10.3390/vaccines7020041 |
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