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nextDART SIGNED

Next-generation Detection of Antigen Responsive T-cells

Total Cost €

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EC-Contrib. €

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Partnership

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Project "nextDART" data sheet

The following table provides information about the project.

Coordinator
DANMARKS TEKNISKE UNIVERSITET 

Organization address
address: ANKER ENGELUNDSVEJ 1 BYGNING 101 A
city: KGS LYNGBY
postcode: 2800
website: www.dtu.dk

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Denmark [DK]
 Total cost 1˙499˙070 €
 EC max contribution 1˙499˙070 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2015-STG
 Funding Scheme ERC-STG
 Starting year 2016
 Duration (year-month-day) from 2016-06-01   to  2021-05-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    DANMARKS TEKNISKE UNIVERSITET DK (KGS LYNGBY) coordinator 1˙499˙070.00

Map

 Project objective

Our current ability to map T-cell reactivity to certain molecular patterns poorly matches the huge diversity of T-cell recognition in humans. Our immune system holds approximately 107 different T-cell populations patrolling our body to fight intruding pathogens. Current state-of-the-art T-cell detection enables the detection of 45 different T-cell specificities in a given sample. Therefore comprehensive analysis of T-cell recognition against intruding pathogens, auto-immune attacked tissues or cancer is virtually impossible. To gain insight into immune recognition and allow careful target selection for disease intervention, also on a personalized basis, we need technologies that allow detection of vast numbers of different T-cell specificities with high sensitivity in small biological samples. I propose here a new technology based on multimerised peptide-major histocompatibility complex I (MHC I) reagents that allow detection of >1000 different T-cell specificities with high sensitivity in small biological samples. I will use this new technology to gain insight into the T-cell recognition of cancer cells and specifically assess the impact of mutation-derived neo-epitopes on T cell-mediated cancer cell recognition. A major advantage of this new technology relates to the ability of coupling the antigen specificity to the T-cell receptor sequence. This will enable us to retrieve information about T-cell receptor sequences coupled with their molecular recognition pattern, and develop a predictor of binding between T-cell receptors and specific epitopes. It will ultimately enable us to predict immune recognition based on T-cell receptor sequences, and has the potential to truly transform our understanding of T cell immunology. Advances in our understanding of T cell immunology are leading to massive advances in the treatment of cancer. The technologies I propose to develop and validate will greatly aid this process and have application for all immune related diseases.

 Publications

year authors and title journal last update
List of publications.
2016 Amalie Kai Bentzen, Andrea Marion Marquard, Rikke Lyngaa, Sunil Kumar Saini, Sofie Ramskov, Marco Donia, Lina Such, Andrew J S Furness, Nicholas McGranahan, Rachel Rosenthal, Per thor Straten, Zoltan Szallasi, Inge Marie Svane, Charles Swanton, Sergio A Quezada, Søren Nyboe Jakobsen, Aron Charles Eklund, Sine Reker Hadrup
Large-scale detection of antigen-specific T cells using peptide-MHC-I multimers labeled with DNA barcodes
published pages: 1037-1045, ISSN: 1087-0156, DOI: 10.1038/nbt.3662
Nature Biotechnology 34/10 2019-07-08
2017 Anne-Mette Bjerregaard, Morten Nielsen, Vanessa Jurtz, Carolina M. Barra, Sine Reker Hadrup, Zoltan Szallasi, Aron Charles Eklund
An Analysis of Natural T Cell Responses to Predicted Tumor Neoepitopes
published pages: , ISSN: 1664-3224, DOI: 10.3389/fimmu.2017.01566
Frontiers in Immunology 8 2019-08-06
2019 Amalie Kai Bentzen, Sine Reker Hadrup
T-cell-receptor cross-recognition and strategies to select safe T-cell receptors for clinical translation
published pages: 1-10, ISSN: 2590-0188, DOI: 10.1016/j.iotech.2019.06.003
Immuno-Oncology Technology 2 2019-08-29
2016 Els M. E. Verdegaal, Noel F. C. C. de Miranda, Marten Visser, Tom Harryvan, Marit M. van Buuren, Rikke S. Andersen, Sine R. Hadrup, Caroline E. van der Minne, Remko Schotte, Hergen Spits, John B. A. G. Haanen, Ellen H. W. Kapiteijn, Ton N. Schumacher, Sjoerd H. van der Burg
Neoantigen landscape dynamics during human melanoma–T cell interactions
published pages: 91-95, ISSN: 0028-0836, DOI: 10.1038/nature18945
Nature 536/7614 2019-08-05
2018 A S Attermann, A -M Bjerregaard, S K Saini, K Grønbæk, S R Hadrup
Human endogenous retroviruses and their implication for immunotherapeutics of cancer
published pages: 2183-2191, ISSN: 0923-7534, DOI: 10.1093/annonc/mdy413
Annals of Oncology 29/11 2019-08-05
2016 N. McGranahan, A. J. S. Furness, R. Rosenthal, S. Ramskov, R. Lyngaa, S. K. Saini, M. Jamal-Hanjani, G. A. Wilson, N. J. Birkbak, C. T. Hiley, T. B. K. Watkins, S. Shafi, N. Murugaesu, R. Mitter, A. U. Akarca, J. Linares, T. Marafioti, J. Y. Henry, E. M. Van Allen, D. Miao, B. Schilling, D. Schadendorf, L. A. Garraway, V. Makarov, N. A. Rizvi, A. Snyder, M. D. Hellmann, T. Merghoub, J. D. Wolchok,
Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade
published pages: 1463-1469, ISSN: 0036-8075, DOI: 10.1126/science.aaf1490
Science 351/6280 2019-08-05
2018 Amalie K Bentzen, Lina Such, Kamilla K Jensen, Andrea M Marquard, Leon E Jessen, Natalie J Miller, Candice D Church, Rikke Lyngaa, David M Koelle, Jürgen C Becker, Carsten Linnemann, Ton N M Schumacher, Paolo Marcatili, Paul Nghiem, Morten Nielsen, Sine R Hadrup
T cell receptor fingerprinting enables in-depth characterization of the interactions governing recognition of peptide–MHC complexes
published pages: 1191-1196, ISSN: 1087-0156, DOI: 10.1038/nbt.4303
Nature Biotechnology 36/12 2019-08-05
2019 Sunil Kumar Saini, Tripti Tamhane, Raghavendra Anjanappa, Ankur Saikia, Sofie Ramskov, Marco Donia, Inge Marie Svane, Søren Nyboe Jakobsen, Maria Garcia-Alai, Martin Zacharias, Rob Meijers, Sebastian Springer, Sine Reker Hadrup
Empty peptide-receptive MHC class I molecules for efficient detection of antigen-specific T cells
published pages: eaau9039, ISSN: 2470-9468, DOI: 10.1126/sciimmunol.aau9039
Science Immunology 4/37 2019-08-29
2017 Sine Reker Hadrup, Evan W. Newell
Determining T-cell specificity to understand and treat disease
published pages: 784-795, ISSN: 2157-846X, DOI: 10.1038/s41551-017-0143-4
Nature Biomedical Engineering 1/10 2019-08-06

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