Antigen targeting to dendritic cells combined with transient regulatory T cell inhibition results in long-term tumor regression.
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Authors
Unger, Wendy WjMayer, Christian T
Engels, Steef
Hesse, Christina
Perdicchio, Maurizio
Puttur, Franz
Streng-Ouwehand, Ingeborg
Litjens, Manja
Kalay, Hakan
Berod, Luciana
Sparwasser, Tim
van Kooyk, Yvette
Issue Date
2015-08
Metadata
Show full item recordAbstract
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.Citation
Antigen targeting to dendritic cells combined with transient regulatory T cell inhibition results in long-term tumor regression. 2015, 4 (8):e970462 OncoimmunologyAffiliation
Institute of Experimental Virology, Twincore, Centre for Experimental and Clinical Infection Research, Hannover, Germany.Journal
OncoimmunologyPubMed ID
26405564Type
ArticleISSN
2162-4011ae974a485f413a2113503eed53cd6c53
10.4161/21624011.2014.970462
Scopus Count
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