TY  - JOUR
A1  - Jamali, Arezoo
A1  - Hadjati, Jamshid
A1  - Madjd, Zahra
A1  - Mirzaei, Hamid Reza
A1  - Thalheimer, Frederic Bastian
A1  - Agarwal, Shiwani
A1  - Bönig, Halvard-Björn
A1  - Ullrich, Evelyn
A1  - Hartmann, Jessica
T1  - Highly efficient generation of transgenically augmented CAR NK cells overexpressing CXCR4
T2  - Frontiers in immunology
N2  - Natural killer (NK) cells are a noteworthy lymphocyte subset in cancer adoptive cell therapy. NK cells initiate innate immune responses against infections and malignancies with natural cytotoxicity, which is independent of foreign antigen recognition. Based on these substantive features, genetically modifying NK cells is among the prime goals in immunotherapy but is currently difficult to achieve. Recently, we reported a fully human CAR19 construct (huCAR19) with remarkable function in gene-modified T-cells. Here, we show efficient and stable gene delivery of huCAR19 to primary human NK cells using lentiviral vectors with transduction efficiencies comparable to those achieved with NK cell lines. These huCAR19 NK cells display specific and potent cytotoxic activity against target cells. To improve homing of NK cells to the bone marrow, we augmented huCAR19 NK cells with the human CXCR4 gene, resulting in transgenically augmented CAR NK cells (TRACKs). Compared to conventional CAR NK cells, TRACKs exhibit enhanced migration capacity in response to recombinant SDF-1 or bone marrow stromal cells while retaining functional and cytolytic activity against target cells. Based on these promising findings, TRACKs may become a novel candidate for immunotherapeutic strategies in clinical applications.
KW  - natural killer cell
KW  - chimeric antigen receptor
KW  - immunotherapy
KW  - fully human
KW  - CAR
KW  - CD19
KW  - huCAR19
KW  - transgenically augmented CAR NK cell
KW  - chemokine receptor 4
Y1  - 2020
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/56058
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-560582
SN  - 1664-3224
VL  - 11
IS  - article 2028
PB  - Frontiers Media
CY  - Lausanne
ER  -