%0 Journal Article %1 johnson2008inhibition %A Johnson, Theron S. %A Mahnke, Karsten %A Storn, Volker %A Schönfeld, Kurt %A Ring, Sabine %A Nettelbeck, Dirk M. %A Haisma, Hidde J. %A Le Gall, Fabrice %A Kontermann, Roland E. %A Enk, Alexander H. %D 2008 %J Clinical Cancer Research %K 2008 izi kontermann %N 24 %P 8169--8177 %R 10.1158/1078-0432.CCR-08-1474 %T Inhibition of melanoma growth by targeting of antigen to dendritic cells via an anti-DEC-205 single-chain fragment variable molecule %U https://www.ncbi.nlm.nih.gov/pubmed/19088032 %V 14 %X PURPOSE: Our goal was to target melanoma antigens to the dendritic cell-specific receptor DEC-205. DEC-205 is an antigen receptor expressed on dendritic cells and has been shown to guide antigens to MHC class I and II compartments for processing and presentation to T cells. EXPERIMENTAL DESIGN: The melanoma tumor-associated antigen (TAA), gp100, was fused to the single-chain fragment variable (scFv) specific for DEC-205. The binding capacity of the scFv was tested on lymph node-isolated CD11c+ cells. Mixed lymphocyte reactions were carried out to show an increased proliferative capacity of gp100 antigen-specific CD4 and CD8 T cells. Furthermore the scFv-TAA was used in a therapeutic setting using two different melanoma mouse models. RESULTS: C57Bl/6 mice were injected with scFv-DEC-205-gp100, monoclonal antibody anti-DEC-205, or PBS. Using fluorescence-activated cell sorting, we showed that lymph node CD11c+ dendritic cells stained positive for the binding of the scFv-mDEC-205-gp100 and the anti-DEC-205 monoclonal antibody, whereas the PBS-injected animals were negative. In mixed lymphocyte reactions, bone marrow-derived dendritic cells pulsed with scFv-mDEC-205-gp100 significantly increased proliferation of gp100-specific CD8+ and CD4+ T cells beyond gp100 peptide-pulsed or nonpulsed bone marrow-derived dendritic cells. Finally, in B16/F10 and RET models, a concentration-dependent suppression of tumor growth using scFv-mDEC-205-gp100 (66\% reduction of tumor volume), in comparison with gp100 peptide vaccination, was observed. CONCLUSIONS: Our results indicate that the scFv-mDEC-205-gp100 targets TAA to dendritic cells in vivo for presentation on both MHC class I and II molecules. In vivo, this leads to an improved immune response and a decrease in tumor growth rate. %@ 4962215663

@article{johnson2008inhibition, abstract = {PURPOSE: Our goal was to target melanoma antigens to the dendritic cell-specific receptor DEC-205. DEC-205 is an antigen receptor expressed on dendritic cells and has been shown to guide antigens to MHC class I and II compartments for processing and presentation to T cells. EXPERIMENTAL DESIGN: The melanoma tumor-associated antigen (TAA), gp100, was fused to the single-chain fragment variable (scFv) specific for DEC-205. The binding capacity of the scFv was tested on lymph node-isolated CD11c+ cells. Mixed lymphocyte reactions were carried out to show an increased proliferative capacity of gp100 antigen-specific CD4 and CD8 T cells. Furthermore the scFv-TAA was used in a therapeutic setting using two different melanoma mouse models. RESULTS: C57Bl/6 mice were injected with scFv-DEC-205-gp100, monoclonal antibody anti-DEC-205, or PBS. Using fluorescence-activated cell sorting, we showed that lymph node CD11c+ dendritic cells stained positive for the binding of the scFv-mDEC-205-gp100 and the anti-DEC-205 monoclonal antibody, whereas the PBS-injected animals were negative. In mixed lymphocyte reactions, bone marrow-derived dendritic cells pulsed with scFv-mDEC-205-gp100 significantly increased proliferation of gp100-specific CD8+ and CD4+ T cells beyond gp100 peptide-pulsed or nonpulsed bone marrow-derived dendritic cells. Finally, in B16/F10 and RET models, a concentration-dependent suppression of tumor growth using scFv-mDEC-205-gp100 (66{\%} reduction of tumor volume), in comparison with gp100 peptide vaccination, was observed. CONCLUSIONS: Our results indicate that the scFv-mDEC-205-gp100 targets TAA to dendritic cells in vivo for presentation on both MHC class I and II molecules. In vivo, this leads to an improved immune response and a decrease in tumor growth rate.}, added-at = {2023-06-29T13:07:55.000+0200}, author = {Johnson, Theron S. and Mahnke, Karsten and Storn, Volker and Sch{\"{o}}nfeld, Kurt and Ring, Sabine and Nettelbeck, Dirk M. and Haisma, Hidde J. and Le Gall, Fabrice and Kontermann, Roland E. and Enk, Alexander H.}, biburl = {https://puma.ub.uni-stuttgart.de/bibtex/2adcdce2c362c0c29288a6ec5c7dbf9d0/fabian}, doi = {10.1158/1078-0432.CCR-08-1474}, interhash = {d7ed36cd5c4af566e2c71abb2cf052db}, intrahash = {adcdce2c362c0c29288a6ec5c7dbf9d0}, isbn = {4962215663}, issn = {10780432}, journal = {Clinical Cancer Research}, keywords = {2008 izi kontermann}, month = dec, number = 24, pages = {8169--8177}, timestamp = {2023-06-29T13:07:55.000+0200}, title = {Inhibition of melanoma growth by targeting of antigen to dendritic cells via an anti-DEC-205 single-chain fragment variable molecule}, url = {https://www.ncbi.nlm.nih.gov/pubmed/19088032}, volume = 14, year = 2008 }