Targeting of DEC-205 on human dendritic cells results in efficient MHC class II-restricted antigen presentation

Birkholz K, Schwenkert M, Kellner C, Gross S, Fey G, Schuler-Thurner B, Schuler G, Schaft N, Dörrie J (2010)

Publication Type: Journal article

Publication year: 2010

Journal

Blood American Society of Hematology

Book Volume: 116

Pages Range: 2277-2285

Journal Issue: 13

DOI: 10.1182/blood-2010-02-268425

Abstract

The use of dendritic cells (DCs) in therapeutic cancer vaccination requires their loading with tumor-specific antigen(s). DEC-205, a phagocytosis receptor mediating antigen uptake, is associated with CD8+ T-cell responses in mice. Here we fused an anti-DEC-205scFv to an HLA-DP4-restricted epitope from the tumor antigen MAGE-A3, and examined the suitability and efficacy of DEC-205 to deliver a helper epitope to human monocytederived DCs (moDCs). The construct specifically bound DEC-205 on human moDCs without negative impact on DC phenotype and function. We measured antigen presentation with specific autologous CD4+ T cells, generated by TCR-RNA transfection. DEC-205 targeting resulted in significant major histocompatibility complex class II-restricted antigen presentation, and was superior to loading DCs by electroporation of mRNA encoding endosome-targeted MAGE-A3-DCLAMP or by direct peptide pulsing. Anti-DEC-205scFv-MAGE-A3 was presented 100 times more efficiently than the control constructs. DC maturation before or during incubation with anti-DEC-205scFv-MAGE-A3 reduced the interleukin-10/interleukin- 2 ratio. Moreover, we successfully applied the DEC-205 targeting strategy to moDCs from malignant melanoma patients. Again, DEC-205-targeted mature DCs (mDCs) presented the antigen more efficiently than peptide-pulsed DCs and maintained their stimulatory capacity after cryoconservation. Thus, DEC-205 targeting represents a feasible and effective method to deliver helper epitopes to DCs in anticancer vaccine strategies, which may also be suitable for DC targeting in vivo. © 2010 by The American Society of Hematology.

Authors with CRIS profile

Georg Fey Naturwissenschaftliche Fakultät Beatrice Schuler-Thurner Lehrstuhl für Haut- und Geschlechtskrankheiten Gerold Schuler Lehrstuhl für Haut- und Geschlechtskrankheiten Niels Schaft Medizinische Fakultät Jan Dörrie Department of Dermatology

Involved external institutions

Christian-Albrechts-Universität zu Kiel DE Germany (DE)

How to cite

APA:

Birkholz, K., Schwenkert, M., Kellner, C., Gross, S., Fey, G., Schuler-Thurner, B.,... Dörrie, J. (2010). Targeting of DEC-205 on human dendritic cells results in efficient MHC class II-restricted antigen presentation. Blood, 116(13), 2277-2285. https://doi.org/10.1182/blood-2010-02-268425

MLA:

Birkholz, Katrin, et al. "Targeting of DEC-205 on human dendritic cells results in efficient MHC class II-restricted antigen presentation." Blood 116.13 (2010): 2277-2285.

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