Combination of immune checkpoint blockade with DNA cancer vaccine induces potent antitumor immunity against P815 mastocytoma

Abstract DNA vaccination against cancer has become a promising strategy for inducing a specific and long-lasting antitumor immunity. However, DNA vaccines fail to generate potent immune responses when used as a single therapy. To enhance their activity into the tumor, a DNA vaccine against murine P8...

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Autores principales:	Alessandra Lopes, Kevin Vanvarenberg, Špela Kos, Sophie Lucas, Didier Colau, Benoît Van den Eynde, Véronique Préat, Gaëlle Vandermeulen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	P815 Mastocytoma Immune Checkpoint Blockers (ICBs) Cancer Vaccination Potent Immune Response Tumor Growth Delay Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8a185f7e782e4e90bd9cd7722f8cbb6c
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spelling	oai:doaj.org-article:8a185f7e782e4e90bd9cd7722f8cbb6c2021-12-02T15:08:36ZCombination of immune checkpoint blockade with DNA cancer vaccine induces potent antitumor immunity against P815 mastocytoma10.1038/s41598-018-33933-72045-2322https://doaj.org/article/8a185f7e782e4e90bd9cd7722f8cbb6c2018-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-33933-7https://doaj.org/toc/2045-2322Abstract DNA vaccination against cancer has become a promising strategy for inducing a specific and long-lasting antitumor immunity. However, DNA vaccines fail to generate potent immune responses when used as a single therapy. To enhance their activity into the tumor, a DNA vaccine against murine P815 mastocytoma was combined with antibodies directed against the immune checkpoints CTLA4 and PD1. The combination of these two strategies delayed tumor growth and enhanced specific antitumor immune cell infiltration in comparison to the corresponding single therapies. The combination also promoted IFNg, IL12 and granzyme B production in the tumor microenvironment and decreased the formation of liver metastasis in a very early phase of tumor development, enabling 90% survival. These results underline the complementarity of DNA vaccination and immune checkpoint blockers in inducing a potent immune response, by exploiting the generation of antigen-specific T cells by the vaccine and the ability of immune checkpoint blockers to enhance T cell activity and infiltration in the tumor. These findings suggest how and why a rational combination therapy can overcome the limits of DNA vaccination but could also allow responses to immune checkpoint blockers in a larger proportion of subjects.Alessandra LopesKevin VanvarenbergŠpela KosSophie LucasDidier ColauBenoît Van den EyndeVéronique PréatGaëlle VandermeulenNature PortfolioarticleP815 MastocytomaImmune Checkpoint Blockers (ICBs)Cancer VaccinationPotent Immune ResponseTumor Growth DelayMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-11 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	P815 Mastocytoma Immune Checkpoint Blockers (ICBs) Cancer Vaccination Potent Immune Response Tumor Growth Delay Medicine R Science Q
spellingShingle	P815 Mastocytoma Immune Checkpoint Blockers (ICBs) Cancer Vaccination Potent Immune Response Tumor Growth Delay Medicine R Science Q Alessandra Lopes Kevin Vanvarenberg Špela Kos Sophie Lucas Didier Colau Benoît Van den Eynde Véronique Préat Gaëlle Vandermeulen Combination of immune checkpoint blockade with DNA cancer vaccine induces potent antitumor immunity against P815 mastocytoma
description	Abstract DNA vaccination against cancer has become a promising strategy for inducing a specific and long-lasting antitumor immunity. However, DNA vaccines fail to generate potent immune responses when used as a single therapy. To enhance their activity into the tumor, a DNA vaccine against murine P815 mastocytoma was combined with antibodies directed against the immune checkpoints CTLA4 and PD1. The combination of these two strategies delayed tumor growth and enhanced specific antitumor immune cell infiltration in comparison to the corresponding single therapies. The combination also promoted IFNg, IL12 and granzyme B production in the tumor microenvironment and decreased the formation of liver metastasis in a very early phase of tumor development, enabling 90% survival. These results underline the complementarity of DNA vaccination and immune checkpoint blockers in inducing a potent immune response, by exploiting the generation of antigen-specific T cells by the vaccine and the ability of immune checkpoint blockers to enhance T cell activity and infiltration in the tumor. These findings suggest how and why a rational combination therapy can overcome the limits of DNA vaccination but could also allow responses to immune checkpoint blockers in a larger proportion of subjects.
format	article
author	Alessandra Lopes Kevin Vanvarenberg Špela Kos Sophie Lucas Didier Colau Benoît Van den Eynde Véronique Préat Gaëlle Vandermeulen
author_facet	Alessandra Lopes Kevin Vanvarenberg Špela Kos Sophie Lucas Didier Colau Benoît Van den Eynde Véronique Préat Gaëlle Vandermeulen
author_sort	Alessandra Lopes
title	Combination of immune checkpoint blockade with DNA cancer vaccine induces potent antitumor immunity against P815 mastocytoma
title_short	Combination of immune checkpoint blockade with DNA cancer vaccine induces potent antitumor immunity against P815 mastocytoma
title_full	Combination of immune checkpoint blockade with DNA cancer vaccine induces potent antitumor immunity against P815 mastocytoma
title_fullStr	Combination of immune checkpoint blockade with DNA cancer vaccine induces potent antitumor immunity against P815 mastocytoma
title_full_unstemmed	Combination of immune checkpoint blockade with DNA cancer vaccine induces potent antitumor immunity against P815 mastocytoma
title_sort	combination of immune checkpoint blockade with dna cancer vaccine induces potent antitumor immunity against p815 mastocytoma
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/8a185f7e782e4e90bd9cd7722f8cbb6c
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Combination of immune checkpoint blockade with DNA cancer vaccine induces potent antitumor immunity against P815 mastocytoma

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