Antigen targeting to dendritic cells combined with transient regulatory T cell inhibition results in long-term tumor regression.

2.50
Hdl Handle:
http://hdl.handle.net/10033/579795
Title:
Antigen targeting to dendritic cells combined with transient regulatory T cell inhibition results in long-term tumor regression.
Authors:
Unger, Wendy Wj; Mayer, Christian T; Engels, Steef; Hesse, Christina; Perdicchio, Maurizio; Puttur, Franz; Streng-Ouwehand, Ingeborg; Litjens, Manja; Kalay, Hakan; Berod, Luciana; Sparwasser, Tim ( 0000-0001-5645-902X ) ; van Kooyk, Yvette
Abstract:
Therapeutic vaccinations against cancer are still largely ineffective. Major caveats are inefficient delivery of tumor antigens to dendritic cells (DCs) and excessive immune suppression by Foxp3(+) regulatory T cells (Tregs), resulting in defective T cell priming and failure to induce tumor regression. To circumvent these problems we evaluated a novel combinatorial therapeutic strategy. We show that tumor antigen targeting to DC-SIGN in humanized hSIGN mice via glycans or specific antibodies induces superior T cell priming. Next, this targeted therapy was combined with transient Foxp3(+) Treg depletion employing hSIGNxDEREG mice. While Treg depletion alone slightly delayed B16-OVA melanoma growth, only the combination therapy instigated long-term tumor regression in a substantial fraction of mice. This novel strategy resulted in optimal generation of antigen-specific activated CD8(+) T cells which accumulated in regressing tumors. Notably, Treg depletion also allowed the local appearance of effector T cells specific for endogenous B16 antigens. This indicates that antitumor immune responses can be broadened by therapies aimed at controlling Tregs in tumor environments. Thus, transient inhibition of Treg-mediated immune suppression potentiates DC targeted antigen vaccination and tumor-specific immunity.
Affiliation:
Institute of Experimental Virology, Twincore, Centre for Experimental and Clinical Infection Research, Hannover, Germany.
Citation:
Antigen targeting to dendritic cells combined with transient regulatory T cell inhibition results in long-term tumor regression. 2015, 4 (8):e970462 Oncoimmunology
Journal:
Oncoimmunology
Issue Date:
Aug-2015
URI:
http://hdl.handle.net/10033/579795
DOI:
10.4161/21624011.2014.970462
PubMed ID:
26405564
Type:
Article
ISSN:
2162-4011
Appears in Collections:
publications of the TwinCore unit Infection immunology

Full metadata record

DC FieldValue Language
dc.contributor.authorUnger, Wendy Wjen
dc.contributor.authorMayer, Christian Ten
dc.contributor.authorEngels, Steefen
dc.contributor.authorHesse, Christinaen
dc.contributor.authorPerdicchio, Maurizioen
dc.contributor.authorPuttur, Franzen
dc.contributor.authorStreng-Ouwehand, Ingeborgen
dc.contributor.authorLitjens, Manjaen
dc.contributor.authorKalay, Hakanen
dc.contributor.authorBerod, Lucianaen
dc.contributor.authorSparwasser, Timen
dc.contributor.authorvan Kooyk, Yvetteen
dc.date.accessioned2015-10-16T13:04:19Zen
dc.date.available2015-10-16T13:04:19Zen
dc.date.issued2015-08en
dc.identifier.citationAntigen targeting to dendritic cells combined with transient regulatory T cell inhibition results in long-term tumor regression. 2015, 4 (8):e970462 Oncoimmunologyen
dc.identifier.issn2162-4011en
dc.identifier.pmid26405564en
dc.identifier.doi10.4161/21624011.2014.970462en
dc.identifier.urihttp://hdl.handle.net/10033/579795en
dc.description.abstractTherapeutic vaccinations against cancer are still largely ineffective. Major caveats are inefficient delivery of tumor antigens to dendritic cells (DCs) and excessive immune suppression by Foxp3(+) regulatory T cells (Tregs), resulting in defective T cell priming and failure to induce tumor regression. To circumvent these problems we evaluated a novel combinatorial therapeutic strategy. We show that tumor antigen targeting to DC-SIGN in humanized hSIGN mice via glycans or specific antibodies induces superior T cell priming. Next, this targeted therapy was combined with transient Foxp3(+) Treg depletion employing hSIGNxDEREG mice. While Treg depletion alone slightly delayed B16-OVA melanoma growth, only the combination therapy instigated long-term tumor regression in a substantial fraction of mice. This novel strategy resulted in optimal generation of antigen-specific activated CD8(+) T cells which accumulated in regressing tumors. Notably, Treg depletion also allowed the local appearance of effector T cells specific for endogenous B16 antigens. This indicates that antitumor immune responses can be broadened by therapies aimed at controlling Tregs in tumor environments. Thus, transient inhibition of Treg-mediated immune suppression potentiates DC targeted antigen vaccination and tumor-specific immunity.en
dc.languageENGen
dc.titleAntigen targeting to dendritic cells combined with transient regulatory T cell inhibition results in long-term tumor regression.en
dc.typeArticleen
dc.contributor.departmentInstitute of Experimental Virology, Twincore, Centre for Experimental and Clinical Infection Research, Hannover, Germany.en
dc.identifier.journalOncoimmunologyen

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