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Enhanced anti-tumor immune responses and delay of tumor development in human epidermal growth factor receptor 2 mice immunized with an immunostimulatory peptide in poly(D,L-lactic-co-glycolic) acid nanoparticles

INTRODUCTION: Cancer vaccines have the potential to induce curative anti-tumor immune responses and better adjuvants may improve vaccine efficacy. We have previously shown that Hp91, a peptide derived from the B box domain in high-mobility group box protein 1 (HMGB1), acts as a potent immune adjuvan...

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Autores principales: Campbell, Diahnn F, Saenz, Rebecca, Bharati, Ila S, Seible, Daniel, Zhang, Liangfang, Esener, Sadik, Messmer, Bradley, Larsson, Marie, Messmer, Davorka
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4407876/
https://www.ncbi.nlm.nih.gov/pubmed/25882711
http://dx.doi.org/10.1186/s13058-015-0552-9
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author Campbell, Diahnn F
Saenz, Rebecca
Bharati, Ila S
Seible, Daniel
Zhang, Liangfang
Esener, Sadik
Messmer, Bradley
Larsson, Marie
Messmer, Davorka
author_facet Campbell, Diahnn F
Saenz, Rebecca
Bharati, Ila S
Seible, Daniel
Zhang, Liangfang
Esener, Sadik
Messmer, Bradley
Larsson, Marie
Messmer, Davorka
author_sort Campbell, Diahnn F
collection PubMed
description INTRODUCTION: Cancer vaccines have the potential to induce curative anti-tumor immune responses and better adjuvants may improve vaccine efficacy. We have previously shown that Hp91, a peptide derived from the B box domain in high-mobility group box protein 1 (HMGB1), acts as a potent immune adjuvant. METHOD: In this study, Hp91 was tested as part of a therapeutic vaccine against human epidermal growth factor receptor 2 (HER2)-positive breast cancer. RESULTS: Free peptide did not significantly augment immune responses but, when delivered in poly(D,L-lactic-co-glycolic) acid nanoparticles (PLGA-NPs), robust activation of dendritic cells (DCs) and increased activation of HER2-specific T cells was observed in vitro. Vaccination of HER2/neu transgenic mice, a mouse breast cancer model that closely mimics the immune modulation and tolerance in some breast cancer patients, with Hp91-loaded PLGA-NPs enhanced the activation of HER2-specific cytotoxic T lymphocyte (CTL) responses, delayed tumor development, and prolonged survival. CONCLUSIONS: Taken together these findings demonstrate that the delivery of the immunostimulatory peptide Hp91 inside PLGA-NPs enhances the potency of the peptide and efficacy of a breast cancer vaccine. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13058-015-0552-9) contains supplementary material, which is available to authorized users.
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spelling pubmed-44078762015-04-24 Enhanced anti-tumor immune responses and delay of tumor development in human epidermal growth factor receptor 2 mice immunized with an immunostimulatory peptide in poly(D,L-lactic-co-glycolic) acid nanoparticles Campbell, Diahnn F Saenz, Rebecca Bharati, Ila S Seible, Daniel Zhang, Liangfang Esener, Sadik Messmer, Bradley Larsson, Marie Messmer, Davorka Breast Cancer Res Research Article INTRODUCTION: Cancer vaccines have the potential to induce curative anti-tumor immune responses and better adjuvants may improve vaccine efficacy. We have previously shown that Hp91, a peptide derived from the B box domain in high-mobility group box protein 1 (HMGB1), acts as a potent immune adjuvant. METHOD: In this study, Hp91 was tested as part of a therapeutic vaccine against human epidermal growth factor receptor 2 (HER2)-positive breast cancer. RESULTS: Free peptide did not significantly augment immune responses but, when delivered in poly(D,L-lactic-co-glycolic) acid nanoparticles (PLGA-NPs), robust activation of dendritic cells (DCs) and increased activation of HER2-specific T cells was observed in vitro. Vaccination of HER2/neu transgenic mice, a mouse breast cancer model that closely mimics the immune modulation and tolerance in some breast cancer patients, with Hp91-loaded PLGA-NPs enhanced the activation of HER2-specific cytotoxic T lymphocyte (CTL) responses, delayed tumor development, and prolonged survival. CONCLUSIONS: Taken together these findings demonstrate that the delivery of the immunostimulatory peptide Hp91 inside PLGA-NPs enhances the potency of the peptide and efficacy of a breast cancer vaccine. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13058-015-0552-9) contains supplementary material, which is available to authorized users. BioMed Central 2015-03-31 2015 /pmc/articles/PMC4407876/ /pubmed/25882711 http://dx.doi.org/10.1186/s13058-015-0552-9 Text en © Campbell et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Campbell, Diahnn F
Saenz, Rebecca
Bharati, Ila S
Seible, Daniel
Zhang, Liangfang
Esener, Sadik
Messmer, Bradley
Larsson, Marie
Messmer, Davorka
Enhanced anti-tumor immune responses and delay of tumor development in human epidermal growth factor receptor 2 mice immunized with an immunostimulatory peptide in poly(D,L-lactic-co-glycolic) acid nanoparticles
title Enhanced anti-tumor immune responses and delay of tumor development in human epidermal growth factor receptor 2 mice immunized with an immunostimulatory peptide in poly(D,L-lactic-co-glycolic) acid nanoparticles
title_full Enhanced anti-tumor immune responses and delay of tumor development in human epidermal growth factor receptor 2 mice immunized with an immunostimulatory peptide in poly(D,L-lactic-co-glycolic) acid nanoparticles
title_fullStr Enhanced anti-tumor immune responses and delay of tumor development in human epidermal growth factor receptor 2 mice immunized with an immunostimulatory peptide in poly(D,L-lactic-co-glycolic) acid nanoparticles
title_full_unstemmed Enhanced anti-tumor immune responses and delay of tumor development in human epidermal growth factor receptor 2 mice immunized with an immunostimulatory peptide in poly(D,L-lactic-co-glycolic) acid nanoparticles
title_short Enhanced anti-tumor immune responses and delay of tumor development in human epidermal growth factor receptor 2 mice immunized with an immunostimulatory peptide in poly(D,L-lactic-co-glycolic) acid nanoparticles
title_sort enhanced anti-tumor immune responses and delay of tumor development in human epidermal growth factor receptor 2 mice immunized with an immunostimulatory peptide in poly(d,l-lactic-co-glycolic) acid nanoparticles
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4407876/
https://www.ncbi.nlm.nih.gov/pubmed/25882711
http://dx.doi.org/10.1186/s13058-015-0552-9
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