Cargando…
Conjugated nanoliposome with the HER2/neu-derived peptide GP2 as an effective vaccine against breast cancer in mice xenograft model
One of the challenging issues in vaccine development is peptide and adjuvant delivery into target cells. In this study, we developed a vaccine and therapeutic delivery system to increase cytotoxic T lymphocyte (CTL) response against a breast cancer model overexpressing HER2/neu. Gp2, a HER2/neu-deri...
Autores principales: | , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5646774/ https://www.ncbi.nlm.nih.gov/pubmed/29045460 http://dx.doi.org/10.1371/journal.pone.0185099 |
_version_ | 1783272144169336832 |
---|---|
author | Razazan, Atefeh Behravan, Javad Arab, Atefeh Barati, Nastaran Arabi, Leila Gholizadeh, Zahra Hatamipour, Mahdi Reza Nikpoor, Amin Momtazi-Borojeni, Amir Abbas Mosaffa, Fatemeh Ghahremani, Mohamad Hosein Jaafari, Mahmoud Reza |
author_facet | Razazan, Atefeh Behravan, Javad Arab, Atefeh Barati, Nastaran Arabi, Leila Gholizadeh, Zahra Hatamipour, Mahdi Reza Nikpoor, Amin Momtazi-Borojeni, Amir Abbas Mosaffa, Fatemeh Ghahremani, Mohamad Hosein Jaafari, Mahmoud Reza |
author_sort | Razazan, Atefeh |
collection | PubMed |
description | One of the challenging issues in vaccine development is peptide and adjuvant delivery into target cells. In this study, we developed a vaccine and therapeutic delivery system to increase cytotoxic T lymphocyte (CTL) response against a breast cancer model overexpressing HER2/neu. Gp2, a HER2/neu-derived peptide, was conjugated to Maleimide-mPEG(2000-)DSPE micelles and post inserted into liposomes composed of DMPC, DMPG phospholipids, and fusogenic lipid dioleoylphosphatidylethanolamine (DOPE) containing monophosphoryl lipid A (MPL) adjuvant (DMPC-DMPG-DOPE-MPL-Gp2). BALB/c mice were immunized with different formulations and the immune response was evaluated in vitro and in vivo. ELISpot and intracellular cytokine analysis by flow cytometry showed that the mice vaccinated with Lip-DOPE-MPL-GP2 incited the highest number of IFN-γ+ in CD8+ cells and CTL response. The immunization led to lower tumor sizes and longer survival time compared to the other groups of mice immunized and treated with the Lip-DOPE-MPL-GP2 formulation in both prophylactic and therapeutic experiments. These results showed that co-formulation of DOPE and MPL conjugated with GP2 peptide not only induces high antitumor immunity but also enhances therapeutic efficacy in TUBO mice model. Lip-DOPE-MPL-GP2 formulation could be a promising vaccine and a therapeutic delivery system against HER2 positive cancers and merits further investigation. |
format | Online Article Text |
id | pubmed-5646774 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-56467742017-10-30 Conjugated nanoliposome with the HER2/neu-derived peptide GP2 as an effective vaccine against breast cancer in mice xenograft model Razazan, Atefeh Behravan, Javad Arab, Atefeh Barati, Nastaran Arabi, Leila Gholizadeh, Zahra Hatamipour, Mahdi Reza Nikpoor, Amin Momtazi-Borojeni, Amir Abbas Mosaffa, Fatemeh Ghahremani, Mohamad Hosein Jaafari, Mahmoud Reza PLoS One Research Article One of the challenging issues in vaccine development is peptide and adjuvant delivery into target cells. In this study, we developed a vaccine and therapeutic delivery system to increase cytotoxic T lymphocyte (CTL) response against a breast cancer model overexpressing HER2/neu. Gp2, a HER2/neu-derived peptide, was conjugated to Maleimide-mPEG(2000-)DSPE micelles and post inserted into liposomes composed of DMPC, DMPG phospholipids, and fusogenic lipid dioleoylphosphatidylethanolamine (DOPE) containing monophosphoryl lipid A (MPL) adjuvant (DMPC-DMPG-DOPE-MPL-Gp2). BALB/c mice were immunized with different formulations and the immune response was evaluated in vitro and in vivo. ELISpot and intracellular cytokine analysis by flow cytometry showed that the mice vaccinated with Lip-DOPE-MPL-GP2 incited the highest number of IFN-γ+ in CD8+ cells and CTL response. The immunization led to lower tumor sizes and longer survival time compared to the other groups of mice immunized and treated with the Lip-DOPE-MPL-GP2 formulation in both prophylactic and therapeutic experiments. These results showed that co-formulation of DOPE and MPL conjugated with GP2 peptide not only induces high antitumor immunity but also enhances therapeutic efficacy in TUBO mice model. Lip-DOPE-MPL-GP2 formulation could be a promising vaccine and a therapeutic delivery system against HER2 positive cancers and merits further investigation. Public Library of Science 2017-10-18 /pmc/articles/PMC5646774/ /pubmed/29045460 http://dx.doi.org/10.1371/journal.pone.0185099 Text en © 2017 Razazan et al http://creativecommons.org/licenses/by/4.0/ 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 author and source are credited. |
spellingShingle | Research Article Razazan, Atefeh Behravan, Javad Arab, Atefeh Barati, Nastaran Arabi, Leila Gholizadeh, Zahra Hatamipour, Mahdi Reza Nikpoor, Amin Momtazi-Borojeni, Amir Abbas Mosaffa, Fatemeh Ghahremani, Mohamad Hosein Jaafari, Mahmoud Reza Conjugated nanoliposome with the HER2/neu-derived peptide GP2 as an effective vaccine against breast cancer in mice xenograft model |
title | Conjugated nanoliposome with the HER2/neu-derived peptide GP2 as an effective vaccine against breast cancer in mice xenograft model |
title_full | Conjugated nanoliposome with the HER2/neu-derived peptide GP2 as an effective vaccine against breast cancer in mice xenograft model |
title_fullStr | Conjugated nanoliposome with the HER2/neu-derived peptide GP2 as an effective vaccine against breast cancer in mice xenograft model |
title_full_unstemmed | Conjugated nanoliposome with the HER2/neu-derived peptide GP2 as an effective vaccine against breast cancer in mice xenograft model |
title_short | Conjugated nanoliposome with the HER2/neu-derived peptide GP2 as an effective vaccine against breast cancer in mice xenograft model |
title_sort | conjugated nanoliposome with the her2/neu-derived peptide gp2 as an effective vaccine against breast cancer in mice xenograft model |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5646774/ https://www.ncbi.nlm.nih.gov/pubmed/29045460 http://dx.doi.org/10.1371/journal.pone.0185099 |
work_keys_str_mv | AT razazanatefeh conjugatednanoliposomewiththeher2neuderivedpeptidegp2asaneffectivevaccineagainstbreastcancerinmicexenograftmodel AT behravanjavad conjugatednanoliposomewiththeher2neuderivedpeptidegp2asaneffectivevaccineagainstbreastcancerinmicexenograftmodel AT arabatefeh conjugatednanoliposomewiththeher2neuderivedpeptidegp2asaneffectivevaccineagainstbreastcancerinmicexenograftmodel AT baratinastaran conjugatednanoliposomewiththeher2neuderivedpeptidegp2asaneffectivevaccineagainstbreastcancerinmicexenograftmodel AT arabileila conjugatednanoliposomewiththeher2neuderivedpeptidegp2asaneffectivevaccineagainstbreastcancerinmicexenograftmodel AT gholizadehzahra conjugatednanoliposomewiththeher2neuderivedpeptidegp2asaneffectivevaccineagainstbreastcancerinmicexenograftmodel AT hatamipourmahdi conjugatednanoliposomewiththeher2neuderivedpeptidegp2asaneffectivevaccineagainstbreastcancerinmicexenograftmodel AT rezanikpooramin conjugatednanoliposomewiththeher2neuderivedpeptidegp2asaneffectivevaccineagainstbreastcancerinmicexenograftmodel AT momtaziborojeniamirabbas conjugatednanoliposomewiththeher2neuderivedpeptidegp2asaneffectivevaccineagainstbreastcancerinmicexenograftmodel AT mosaffafatemeh conjugatednanoliposomewiththeher2neuderivedpeptidegp2asaneffectivevaccineagainstbreastcancerinmicexenograftmodel AT ghahremanimohamadhosein conjugatednanoliposomewiththeher2neuderivedpeptidegp2asaneffectivevaccineagainstbreastcancerinmicexenograftmodel AT jaafarimahmoudreza conjugatednanoliposomewiththeher2neuderivedpeptidegp2asaneffectivevaccineagainstbreastcancerinmicexenograftmodel |