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Generation of safe and efficient, off-the-shelf, chimeric antigen receptor (CAR)-engineered T cells for broad application

Total Cost €


EC-Contrib. €






Project "CARiPSCTcells" data sheet

The following table provides information about the project.


Organization address
address: DE BOELELAAN 1117
postcode: 1081 HV

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 Netherlands [NL]
 Total cost 165˙598 €
 EC max contribution 165˙598 € (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-RI
 Starting year 2015
 Duration (year-month-day) from 2015-07-01   to  2017-06-30


Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    STICHTING VUMC NL (AMSTERDAM) coordinator 123˙279.00
2    STICHTING VU NL (AMSTERDAM) participant 42˙319.00


 Project objective

The feasibility and effectiveness of adoptive T cell therapies for cancer has now been proven in several clinical settings. Yet, the current approaches are still “individual-tailored” and thus, their progress and broader use is limited. Having rapid access to “off-the-shelf”, safe cellular products, which can be applied across histocompatibility limitations, would greatly benefit the broader applicability of adoptive T cell therapy. To this end, the applicant recently reported, in a proof-of-concept study, that genetic engineering of T-cell derived induced pluripotent stem cells (TiPSC) with Chimeric Antigen Receptors (CARs) can be an efficient strategy to concomitantly harness the unlimited availability of induced pluripotent stem cells and direct the specificity and functional potential of TiPSC-derived T cells in an HLA-independent manner. Based on this technology, this proposal aims to further investigate novel stem cell genetic engineering strategies in order to obtain in vitro, unlimited, safe and broadly applicable T cells targeting Multiple Myeloma (MM). We propose to target MM with a novel CD38-targeting CAR (CD38CAR). Since CD38 is not a MM-specific target, we aim to simultaneously tackle the on-target/off-tumor toxicity by introducing a drug-regulated expression of CD38CAR. In addition, we aim to use the CRISPR/Cas9 system to achieve targeted knockout of the endogenous T cell receptor (TCR) and the HLA antigens on the CAR-engineered TiPSCs (CARTiPSC) in order to extend the applicability of CARTiPSC-derived T cells across HLA-barriers. The success of this proposal will lay the foundation for further translational application of CARTiPSC-derived T cells cells and investigation of new strategies to enhance their effector function and persistence.


year authors and title journal last update
List of publications.
2017 Esther Drent, Maria Themeli, Renée Poels, Regina de Jong-Korlaar, Huipin Yuan, Joost de Bruijn, Anton C.M. Martens, Sonja Zweegman, Niels W.C.J. van de Donk, Richard W.J. Groen, Henk M. Lokhorst, Tuna Mutis
A Rational Strategy for Reducing On-Target Off-Tumor Effects of CD38-Chimeric Antigen Receptors by Affinity Optimization
published pages: , ISSN: 1525-0016, DOI: 10.1016/j.ymthe.2017.04.024
Molecular Therapy 2019-06-14

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