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

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.

Field of science

  • /medical and health sciences/medical biotechnology/cells technologies/stem cells
  • /medical and health sciences/clinical medicine/oncology/cancer
  • /medical and health sciences/medical biotechnology/genetic engineering

Call for proposal

H2020-MSCA-IF-2014
See other projects for this call

Funding Scheme

MSCA-IF-EF-RI - RI – Reintegration panel

Coordinator

STICHTING VUMC
Address
De Boelelaan 1117
1081 HV Amsterdam
Netherlands
Activity type
Research Organisations
EU contribution
€ 123 279,33

Participants (1)

STICHTING VU

Participation ended

Netherlands
EU contribution
€ 42 319,47
Address
De Boelelaan 1105
1081 HV Amsterdam
Activity type
Higher or Secondary Education Establishments