Cel 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. Dziedzina nauki medical and health sciencesmedical biotechnologygenetic engineeringgene therapymedical and health sciencesmedical biotechnologycells technologiesstem cellsmedical and health sciencesclinical medicineoncologymedical and health sciencesbasic medicineimmunologyimmunotherapymedical and health sciencesclinical medicinetransplantation Program(-y) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Temat(-y) MSCA-IF-2014-EF - Marie Skłodowska-Curie Individual Fellowships (IF-EF) Zaproszenie do składania wniosków H2020-MSCA-IF-2014 Zobacz inne projekty w ramach tego zaproszenia System finansowania MSCA-IF-EF-RI - RI – Reintegration panel Koordynator STICHTING AMSTERDAM UMC Wkład UE netto € 123 279,33 Adres DE BOELELAAN 1117 1081 HV Amsterdam Niderlandy Zobacz na mapie Region West-Nederland Noord-Holland Groot-Amsterdam Rodzaj działalności Research Organisations Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Uczestnictwo w unijnych programach w zakresie badań i innowacji Opens in new window sieć współpracy HORIZON Opens in new window Koszt całkowity € 123 279,34 Uczestnicy (1) Sortuj alfabetycznie Sortuj według wkładu UE netto Rozwiń wszystko Zwiń wszystko STICHTING VU Zakończenie uczestnictwa Niderlandy Wkład UE netto € 42 319,47 Adres DE BOELELAAN 1105 1081 HV Amsterdam Zobacz na mapie Region West-Nederland Noord-Holland Groot-Amsterdam Rodzaj działalności Higher or Secondary Education Establishments Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Uczestnictwo w unijnych programach w zakresie badań i innowacji Opens in new window sieć współpracy HORIZON Opens in new window Koszt całkowity € 42 319,47