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CARiPSCTcells

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

Total Cost €

EC-Contrib. €

Partnership

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Outcomes and
results

CARiPSCTcells project word cloud

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

applicable car expression obtain introducing tipsc cars antigen off limitations vitro persistence cartipsc effector effectiveness benefit drug extend cd38 myeloma regulated individual barriers hla stem cas9 broadly independent tackle toxicity cellular translational adoptive endogenous shelf progress safe engineered proven tipscs genetic simultaneously concomitantly therapies rapid cancer strategy cells settings manner proof mm strategies multiple feasibility foundation tumor chimeric efficient unlimited direct receptor tcr therapy function pluripotent cd38car receptors lay clinical harness crispr applicability antigens limited investigation histocompatibility functional cell engineering specificity reported knockout

Project "CARiPSCTcells" data sheet

The following table provides information about the project.

Coordinator	STICHTING VUMC Organization address address: DE BOELELAAN 1117 city: AMSTERDAM postcode: 1081 HV website: www.vumc.nl 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

Partnership

Take a look of project's partnership.

#	participants	country	role	EC contrib. [€]
1	STICHTING VUMC STICHTING VUMC Organization address address: DE BOELELAAN 1117 city: AMSTERDAM postcode: 1081 HV website: www.vumc.nl contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	NL (AMSTERDAM)	coordinator	123˙279.00
2	STICHTING VU STICHTING VU Organization address address: DE BOELELAAN 1105 city: AMSTERDAM postcode: 1081 HV website: www.vu.nl contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	NL (AMSTERDAM)	participant	42˙319.00

Map

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.

Publications

List of publications.
year	authors and title	journal	last update
2017	Esther Drent, Maria Themeli, RenÃ©e 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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The information about "CARIPSCTCELLS" are provided by the European Opendata Portal: CORDIS opendata.