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TIPPDECRA SIGNED

Tolerogenic immunotherapy with peptide-pulsed dendritic cells in rheumatoid arthritis

Total Cost €

EC-Contrib. €

Partnership

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Outcomes and
results

TIPPDECRA project word cloud

Explore the words cloud of the TIPPDECRA project. It provides you a very rough idea of what is the project "TIPPDECRA" about.

arthritis tolerance me peptide exogenous patients model destructive safe off allergy induce utrecht selecting peptides newcastle therapy synovium found kingdom dendritic pathogenic translational benefit ubiquitously university united hypothesise proteins hsp loaded team acquire loading cells expertise clinical phd successful immune netherlands models immunology auto regulatory immunotherapy hsps antigen human rheumatoid host form designed mouse antigens after efficacy move suitable la tolerogenic obtaining conduct san diego expressed suppressed ra therapeutic induction jolla postdoc disease toldc trial joint switch synthetic outcome shock moved cell basis heat

Project "TIPPDECRA" data sheet

The following table provides information about the project.

Coordinator	UNIVERSITY OF NEWCASTLE UPON TYNE Organization address address: KINGS GATE city: NEWCASTLE UPON TYNE postcode: NE1 7RU website: http://www.ncl.ac.uk/ 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	United Kingdom [UK]
Total cost	183˙454 €
EC max contribution	183˙454 € (100%)
Programme	1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
Code Call	H2020-MSCA-IF-2014
Funding Scheme	MSCA-IF-EF-ST
Starting year	2016
Duration (year-month-day)	from 2016-05-05 to 2018-05-04

Partnership

Take a look of project's partnership.

#	participants	country	role	EC contrib. [€]
1	UNIVERSITY OF NEWCASTLE UPON TYNE UNIVERSITY OF NEWCASTLE UPON TYNE Organization address address: KINGS GATE city: NEWCASTLE UPON TYNE postcode: NE1 7RU website: http://www.ncl.ac.uk/ contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	UK (NEWCASTLE UPON TYNE)	coordinator	183˙454.00

Map

Project objective

After obtaining my PhD at the University of Utrecht in the Netherlands, I moved to San Diego for a 1-year postdoc at the La Jolla Institute for Allergy and Immunology. I now propose to move to Newcastle University in the United Kingdom to undertake a project on a new cell-based therapy for rheumatoid arthritis (RA), a destructive joint disease. This project is important since this new therapy could provide long-term benefit to RA patients. So far I have conducted all my work in mouse models. This project will enable me to acquire new expertise in human immunology and translational research. The host team at Newcastle University has developed a new immunotherapy for RA with tolerogenic dendritic cells (tolDC). These tolDC have been designed to switch-off destructive immune responses in the joint via the induction of regulatory T cells. The team has completed a phase I trial with tolDC in RA, and has found that the therapy is safe. However, in order to conduct a phase II efficacy trial, one crucial aspect of tolDC therapy must be improved: loading of tolDC with a relevant (auto)antigen so that they can induce antigen-specific regulatory T cells in the joint. However, selecting a suitable auto-antigen has been problematic. I propose that heat shock proteins (HSPs) are suitable antigens for loading of tolDC. HSPs are ubiquitously expressed in the rheumatoid synovium and pathogenic T-cell responses to these HSPs are found in RA patients. I hypothesise that by loading tolDC with exogenous synthetic peptides from HSPs, the pathogenic response can be suppressed through the induction of HSP-specific regulatory T cells. My project aims to i) establish a suitable HSP-peptide selection for tolDC-induced peptide-specific tolerance in RA patients and ii) test the therapeutic potential of HSP-peptide-loaded tolDC in a mouse arthritis model. A successful outcome of this work would form the basis of a new clinical trial with HSP-loaded tolDC in RA patients.

Publications

List of publications.
year	authors and title	journal	last update
2018	Manon A. A. Jansen, Rachel Spiering, Femke Broere, Jacob M. van Laar, John D. Isaacs, Willem van Eden, Catharien M. U. Hilkens Targeting of tolerogenic dendritic cells towards heat-shock proteins: a novel therapeutic strategy for autoimmune diseases? published pages: 51-59, ISSN: 0019-2805, DOI: 10.1111/imm.12811	Immunology 153/1	2019-06-13

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