Booster immunizations with DNA plasmids encoding HER-2/neu prevent spontaneous mammary cancer in HER-2/neu transgenic mice over life span

Abstract Cancer vaccines are less effective at old than at young age because of immunosenescence. Besides, in preliminary observations we showed that the immunization with HER-2/neu DNA plasmid in transgenic young mice (standard immunization, SI) delays but not abrogate spontaneous mammary tumours p...

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Autores principales: Mauro Provinciali, Alessandra Barucca, Fiorenza Orlando, Elisa Pierpaoli
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Publicado: Nature Portfolio 2017
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spelling oai:doaj.org-article:30a26d3f0af04239af09033dd04f3b152021-12-02T11:52:36ZBooster immunizations with DNA plasmids encoding HER-2/neu prevent spontaneous mammary cancer in HER-2/neu transgenic mice over life span10.1038/s41598-017-03286-82045-2322https://doaj.org/article/30a26d3f0af04239af09033dd04f3b152017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03286-8https://doaj.org/toc/2045-2322Abstract Cancer vaccines are less effective at old than at young age because of immunosenescence. Besides, in preliminary observations we showed that the immunization with HER-2/neu DNA plasmid in transgenic young mice (standard immunization, SI) delays but not abrogate spontaneous mammary tumours progressively appearing during aging. In this study we evaluated whether booster immunizations (BI) of HER-2/neu transgenic mice with HER-2/neu DNA plasmids every 6 (ECD6), 3 (ECD3), or 1.5 (ECD1.5) months after SI induce a protective immunity that could be maintained over life span. The long term BI significantly improved the effect of SI increasing the number of tumour free mice at 110 weeks of age from 13% (SI) to 58% (BI). Both the number and the volume of tumour masses were reduced in BI than in SI groups. The protective effect of BI was associated with increased antibody production with isotype switching to IgG2a, augmented CD4 T cells, and increased in vivo cytotoxicity of HER-2/neu specific cytotoxic T lymphocytes, mainly in ECD1.5 and ECD3 groups. The transfer of sera from ECD1.5 mice to untreated HER-2/neu mice highly protected against tumour development than sera from SI mice. We conclude that BI induce a protective immunity effective over life span.Mauro ProvincialiAlessandra BaruccaFiorenza OrlandoElisa PierpaoliNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Mauro Provinciali
Alessandra Barucca
Fiorenza Orlando
Elisa Pierpaoli
Booster immunizations with DNA plasmids encoding HER-2/neu prevent spontaneous mammary cancer in HER-2/neu transgenic mice over life span
description Abstract Cancer vaccines are less effective at old than at young age because of immunosenescence. Besides, in preliminary observations we showed that the immunization with HER-2/neu DNA plasmid in transgenic young mice (standard immunization, SI) delays but not abrogate spontaneous mammary tumours progressively appearing during aging. In this study we evaluated whether booster immunizations (BI) of HER-2/neu transgenic mice with HER-2/neu DNA plasmids every 6 (ECD6), 3 (ECD3), or 1.5 (ECD1.5) months after SI induce a protective immunity that could be maintained over life span. The long term BI significantly improved the effect of SI increasing the number of tumour free mice at 110 weeks of age from 13% (SI) to 58% (BI). Both the number and the volume of tumour masses were reduced in BI than in SI groups. The protective effect of BI was associated with increased antibody production with isotype switching to IgG2a, augmented CD4 T cells, and increased in vivo cytotoxicity of HER-2/neu specific cytotoxic T lymphocytes, mainly in ECD1.5 and ECD3 groups. The transfer of sera from ECD1.5 mice to untreated HER-2/neu mice highly protected against tumour development than sera from SI mice. We conclude that BI induce a protective immunity effective over life span.
format article
author Mauro Provinciali
Alessandra Barucca
Fiorenza Orlando
Elisa Pierpaoli
author_facet Mauro Provinciali
Alessandra Barucca
Fiorenza Orlando
Elisa Pierpaoli
author_sort Mauro Provinciali
title Booster immunizations with DNA plasmids encoding HER-2/neu prevent spontaneous mammary cancer in HER-2/neu transgenic mice over life span
title_short Booster immunizations with DNA plasmids encoding HER-2/neu prevent spontaneous mammary cancer in HER-2/neu transgenic mice over life span
title_full Booster immunizations with DNA plasmids encoding HER-2/neu prevent spontaneous mammary cancer in HER-2/neu transgenic mice over life span
title_fullStr Booster immunizations with DNA plasmids encoding HER-2/neu prevent spontaneous mammary cancer in HER-2/neu transgenic mice over life span
title_full_unstemmed Booster immunizations with DNA plasmids encoding HER-2/neu prevent spontaneous mammary cancer in HER-2/neu transgenic mice over life span
title_sort booster immunizations with dna plasmids encoding her-2/neu prevent spontaneous mammary cancer in her-2/neu transgenic mice over life span
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/30a26d3f0af04239af09033dd04f3b15
work_keys_str_mv AT mauroprovinciali boosterimmunizationswithdnaplasmidsencodingher2neupreventspontaneousmammarycancerinher2neutransgenicmiceoverlifespan
AT alessandrabarucca boosterimmunizationswithdnaplasmidsencodingher2neupreventspontaneousmammarycancerinher2neutransgenicmiceoverlifespan
AT fiorenzaorlando boosterimmunizationswithdnaplasmidsencodingher2neupreventspontaneousmammarycancerinher2neutransgenicmiceoverlifespan
AT elisapierpaoli boosterimmunizationswithdnaplasmidsencodingher2neupreventspontaneousmammarycancerinher2neutransgenicmiceoverlifespan
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