Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Nika, Lisa, Cuadrado-Castano, Sara, Asthagiri Arunkumar, Guha, Grünwald-Gruber, Clemens, McMahon, Meagan, Koczka, Krisztina, García-Sastre, Adolfo, Krammer, Florian, Grabherr, Reingard
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
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
_version_ 1783435545840451584
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
work_keys_str_mv AT nikalisa aher2displayingviruslikeparticlevaccineprotectsfromchallengewithmammarycarcinomacellsinamousemodel
AT cuadradocastanosara aher2displayingviruslikeparticlevaccineprotectsfromchallengewithmammarycarcinomacellsinamousemodel
AT asthagiriarunkumarguha aher2displayingviruslikeparticlevaccineprotectsfromchallengewithmammarycarcinomacellsinamousemodel
AT grunwaldgruberclemens aher2displayingviruslikeparticlevaccineprotectsfromchallengewithmammarycarcinomacellsinamousemodel
AT mcmahonmeagan aher2displayingviruslikeparticlevaccineprotectsfromchallengewithmammarycarcinomacellsinamousemodel
AT koczkakrisztina aher2displayingviruslikeparticlevaccineprotectsfromchallengewithmammarycarcinomacellsinamousemodel
AT garciasastreadolfo aher2displayingviruslikeparticlevaccineprotectsfromchallengewithmammarycarcinomacellsinamousemodel
AT krammerflorian aher2displayingviruslikeparticlevaccineprotectsfromchallengewithmammarycarcinomacellsinamousemodel
AT grabherrreingard aher2displayingviruslikeparticlevaccineprotectsfromchallengewithmammarycarcinomacellsinamousemodel
AT nikalisa her2displayingviruslikeparticlevaccineprotectsfromchallengewithmammarycarcinomacellsinamousemodel
AT cuadradocastanosara her2displayingviruslikeparticlevaccineprotectsfromchallengewithmammarycarcinomacellsinamousemodel
AT asthagiriarunkumarguha her2displayingviruslikeparticlevaccineprotectsfromchallengewithmammarycarcinomacellsinamousemodel
AT grunwaldgruberclemens her2displayingviruslikeparticlevaccineprotectsfromchallengewithmammarycarcinomacellsinamousemodel
AT mcmahonmeagan her2displayingviruslikeparticlevaccineprotectsfromchallengewithmammarycarcinomacellsinamousemodel
AT koczkakrisztina her2displayingviruslikeparticlevaccineprotectsfromchallengewithmammarycarcinomacellsinamousemodel
AT garciasastreadolfo her2displayingviruslikeparticlevaccineprotectsfromchallengewithmammarycarcinomacellsinamousemodel
AT krammerflorian her2displayingviruslikeparticlevaccineprotectsfromchallengewithmammarycarcinomacellsinamousemodel
AT grabherrreingard her2displayingviruslikeparticlevaccineprotectsfromchallengewithmammarycarcinomacellsinamousemodel