Crosstag SIGNED
Unravelling cross-presentation pathways using a chemical biology approach
Total Cost €
0EC-Contrib. €
0Partnership
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Project "Crosstag" data sheet
The following table provides information about the project.
| Coordinator |
UNIVERSITEIT LEIDEN
Organization address contact info |
| Coordinator Country | Netherlands [NL] |
| Project website | https://www.universiteitleiden.nl/en/staffmembers/sander-van-kasteren |
| Total cost | 1˙500˙000 € |
| EC max contribution | 1˙500˙000 € (100%) |
| Programme |
1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC)) |
| Code Call | ERC-2014-STG |
| Funding Scheme | ERC-STG |
| Starting year | 2015 |
| Duration (year-month-day) | from 2015-05-01 to 2020-04-30 |
Partnership
Take a look of project's partnership.
| # | ||||
|---|---|---|---|---|
| 1 | UNIVERSITEIT LEIDEN | NL (LEIDEN) | coordinator | 1˙500˙000.00 |
Map
Project objective
Immune therapies are therefore currently being pursued to reinvigorate the immune reaction against tumours. This is not trivial, as the right type of immune cells must be activated against a tumour-specific antigen. One method to achieve this is by targeting tumour antigens to certain cross-presentation-promoting receptors on antigen presenting cells. The most intriguing of these is the mannose receptor (MR) as the method by which it does this is unknown. This glycoprotein-binding receptor appears to have two functions on APCs: general uptake-enhancement and, in certain isolated cases, cross-presentation-enhancment. What ligand parameters are important in causing cross-presentation enhancement is not known. Current tools, such as anti-MR antibodies and randomly glycosylated ligands fail to selectively enhance cross-presentation. The main aim of this proposal is to determine what structural parameters of the glycoprotein antigen result in enhanced cross-presentation upon MR-ligation. I will synthesise a library of biologically traceable single glycoform ligands - with controlled variation in glycan nature, stoichiometry and positioning - for the MR and study differences in uptake, routing and antigen presentation. A 2nd aim is to uncover what happens to the antigen after uptake by the MR. I.e. whether changes in antigen routing and proteolysis are responsible for enhanced cross presentation of different glycoforms. A 3rd aim is to develop a new method to study the kinetics of surface appearance of epitopes without T-cell reagents to quantify differences between glycoforms. With this approach I aim to gain new insight into methods for enhancing cross-presentation resulting in improved immune therapies against cancer. My background in carbohydrate and protein modification chemistry will provide the toolkit to synthesise the relevant reagents and my background in immunology will ensure the successful immunological validation of the synthetic single glycoforms.
Publications
| year | authors and title | journal | last update |
|---|---|---|---|
| 2018 |
Thomas Bakkum, Tyrza van Leeuwen, Alexi J. C. Sarris, Daphne M. van Elsland, Dimitrios Poulcharidis, Herman S. Overkleeft, Sander I. van Kasteren Quantification of Bioorthogonal Stability in Immune Phagocytes Using Flow Cytometry Reveals Rapid Degradation of Strained Alkynes published pages: 1173-1179, ISSN: 1554-8929, DOI: 10.1021/acschembio.8b00355 |
ACS Chemical Biology 13/5 | 2019-12-16 |
| 2017 |
Timo Oosenbrug, Michel J. van de Graaff, Maaike E. Ressing, Sander I. van Kasteren Chemical Tools for Studying TLR Signaling Dynamics published pages: 801-812, ISSN: 2451-9456, DOI: 10.1016/j.chembiol.2017.05.022 |
Cell Chemical Biology 24/7 | 2019-12-16 |
| 2016 |
Daphne M. van Elsland, Sander I. van Kasteren Imaging Bioorthogonal Groups in Their Ultrastructural Context with Electron Microscopy published pages: 9472-9473, ISSN: 1433-7851, DOI: 10.1002/anie.201604672 |
Angewandte Chemie International Edition 55/33 | 2019-12-16 |
| 2017 |
Dimitrios Poulcharidis, Kimberley Belfor, Alexander Kros, Sander I. van Kasteren A flow cytometry assay to quantify intercellular exchange of membrane components published pages: 5585-5590, ISSN: 2041-6520, DOI: 10.1039/c7sc00260b |
Chemical Science 8/8 | 2019-12-16 |
| 2016 |
Frank Versluis, Daphne M. van Elsland, Serhii Mytnyk, Dayinta L. Perrier, Fanny Trausel, Jos M. Poolman, Chandan Maity, Vincent A. A. le Sage, Sander I. van Kasteren, Jan H. van Esch, Rienk Eelkema Negatively Charged Lipid Membranes Catalyze Supramolecular Hydrogel Formation published pages: 8670-8673, ISSN: 0002-7863, DOI: 10.1021/jacs.6b03853 |
Journal of the American Chemical Society 138/28 | 2019-05-29 |
| 2016 |
S. Anwar Jagessar, Inge R. Holtman, Sam Hofman, Elena Morandi, Nicole Heijmans, Jon D. Laman, Bruno Gran, Bart W. Faber, Sander I. van Kasteren, Bart J. L. Eggen, Bert A. ‘t Hart Lymphocryptovirus Infection of Nonhuman Primate B Cells Converts Destructive into Productive Processing of the Pathogenic CD8 T Cell Epitope in Myelin Oligodendrocyte Glycoprotein published pages: 1074-1088, ISSN: 0022-1767, DOI: 10.4049/jimmunol.1600124 |
The Journal of Immunology 197/4 | 2019-05-29 |
| 2016 |
Joanna B. Pawlak, Brett J. Hos, Michel J. van de Graaff, Otty A. Megantari, Nico Meeuwenoord, Herman S. Overkleeft, Dmitri V. Filippov, Ferry Ossendorp, Sander I. van Kasteren The Optimization of Bioorthogonal Epitope Ligation within MHC-I Complexes published pages: 3172-3178, ISSN: 1554-8929, DOI: 10.1021/acschembio.6b00498 |
ACS Chemical Biology 11/11 | 2019-05-29 |
| 2016 |
Daphne M. van Elsland, Erik Bos, Wouter de Boer, Herman S. Overkleeft, Abraham J. Koster, Sander I. van Kasteren Detection of bioorthogonal groups by correlative light and electron microscopy allows imaging of degraded bacteria in phagocytes published pages: 752-758, ISSN: 2041-6520, DOI: 10.1039/C5SC02905H |
Chem. Sci. 7/1 | 2019-05-29 |
| 2015 |
Joanna B. Pawlak, Geoffroy P. P. Gential, Tracy J. Ruckwardt, Jessica S. Bremmers, Nico J. Meeuwenoord, Ferry A. Ossendorp, Herman S. Overkleeft, Dmitri V. Filippov, Sander I. van Kasteren Bioorthogonal Deprotection on the Dendritic Cell Surface for Chemical Control of Antigen Cross-Presentation published pages: 5628-5631, ISSN: 1433-7851, DOI: 10.1002/anie.201500301 |
Angewandte Chemie International Edition 54/19 | 2019-05-29 |
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