Route of administration of the TLR9 agonist CpG critically determines the efficacy of cancer immunotherapy in mice.

<h4>Background</h4>The TLR9 agonist CpG is increasingly applied in preclinical and clinical studies as a therapeutic modality to enhance tumor immunity. The clinical application of CpG appears, however, less successful than would be predicted from animal studies. One reason might be the...

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Autores principales:	Stefan Nierkens, Martijn H den Brok, Thijs Roelofsen, Jori A L Wagenaars, Carl G Figdor, Theo J Ruers, Gosse J Adema
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9b71579ac2cc4de8ab648b64648303bf
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spelling	oai:doaj.org-article:9b71579ac2cc4de8ab648b64648303bf2021-11-25T06:27:17ZRoute of administration of the TLR9 agonist CpG critically determines the efficacy of cancer immunotherapy in mice.1932-620310.1371/journal.pone.0008368https://doaj.org/article/9b71579ac2cc4de8ab648b64648303bf2009-12-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20020049/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>The TLR9 agonist CpG is increasingly applied in preclinical and clinical studies as a therapeutic modality to enhance tumor immunity. The clinical application of CpG appears, however, less successful than would be predicted from animal studies. One reason might be the different administration routes applied in most mouse studies and clinical trials. We studied whether the efficacy of CpG as an adjuvant in cancer immunotherapy is dependent on the route of CpG administration, in particular when the tumor is destructed in situ.<h4>Methodology/principal findings</h4>In situ tumor destruction techniques are minimally invasive therapeutic alternatives for the treatment of (nonresectable) solid tumors. In contrast to surgical resection, tumor destruction leads to the induction of weak but tumor-specific immunity that can be enhanced by coapplication of CpG. As in situ tumor destruction by cryosurgery creates an instant local release of antigens, we applied this model to study the efficacy of CpG to enhance antitumor immunity when administrated via different routes: peritumoral, intravenous, and subcutaneous but distant from the tumor. We show that peritumoral administration is superior in the activation of dendritic cells, induction of tumor-specific CTL, and long-lasting tumor protection. Although the intravenous and subcutaneous (at distant site) exposures are commonly used in clinical trials, they only provided partial protection or even failed to enhance antitumor responses as induced by cryosurgery alone.<h4>Conclusions/significance</h4>CpG administration greatly enhances the efficacy of in situ tumor destruction techniques, provided that CpG is administered in close proximity of the released antigens. Hence, this study helps to provide directions to fully benefit from CpG as immune stimulant in a clinical setting.Stefan NierkensMartijn H den BrokThijs RoelofsenJori A L WagenaarsCarl G FigdorTheo J RuersGosse J AdemaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 4, Iss 12, p e8368 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Stefan Nierkens Martijn H den Brok Thijs Roelofsen Jori A L Wagenaars Carl G Figdor Theo J Ruers Gosse J Adema Route of administration of the TLR9 agonist CpG critically determines the efficacy of cancer immunotherapy in mice.
description	<h4>Background</h4>The TLR9 agonist CpG is increasingly applied in preclinical and clinical studies as a therapeutic modality to enhance tumor immunity. The clinical application of CpG appears, however, less successful than would be predicted from animal studies. One reason might be the different administration routes applied in most mouse studies and clinical trials. We studied whether the efficacy of CpG as an adjuvant in cancer immunotherapy is dependent on the route of CpG administration, in particular when the tumor is destructed in situ.<h4>Methodology/principal findings</h4>In situ tumor destruction techniques are minimally invasive therapeutic alternatives for the treatment of (nonresectable) solid tumors. In contrast to surgical resection, tumor destruction leads to the induction of weak but tumor-specific immunity that can be enhanced by coapplication of CpG. As in situ tumor destruction by cryosurgery creates an instant local release of antigens, we applied this model to study the efficacy of CpG to enhance antitumor immunity when administrated via different routes: peritumoral, intravenous, and subcutaneous but distant from the tumor. We show that peritumoral administration is superior in the activation of dendritic cells, induction of tumor-specific CTL, and long-lasting tumor protection. Although the intravenous and subcutaneous (at distant site) exposures are commonly used in clinical trials, they only provided partial protection or even failed to enhance antitumor responses as induced by cryosurgery alone.<h4>Conclusions/significance</h4>CpG administration greatly enhances the efficacy of in situ tumor destruction techniques, provided that CpG is administered in close proximity of the released antigens. Hence, this study helps to provide directions to fully benefit from CpG as immune stimulant in a clinical setting.
format	article
author	Stefan Nierkens Martijn H den Brok Thijs Roelofsen Jori A L Wagenaars Carl G Figdor Theo J Ruers Gosse J Adema
author_facet	Stefan Nierkens Martijn H den Brok Thijs Roelofsen Jori A L Wagenaars Carl G Figdor Theo J Ruers Gosse J Adema
author_sort	Stefan Nierkens
title	Route of administration of the TLR9 agonist CpG critically determines the efficacy of cancer immunotherapy in mice.
title_short	Route of administration of the TLR9 agonist CpG critically determines the efficacy of cancer immunotherapy in mice.
title_full	Route of administration of the TLR9 agonist CpG critically determines the efficacy of cancer immunotherapy in mice.
title_fullStr	Route of administration of the TLR9 agonist CpG critically determines the efficacy of cancer immunotherapy in mice.
title_full_unstemmed	Route of administration of the TLR9 agonist CpG critically determines the efficacy of cancer immunotherapy in mice.
title_sort	route of administration of the tlr9 agonist cpg critically determines the efficacy of cancer immunotherapy in mice.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/9b71579ac2cc4de8ab648b64648303bf
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Route of administration of the TLR9 agonist CpG critically determines the efficacy of cancer immunotherapy in mice.

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