Highly efficient generation of transgenically augmented CAR NK cells overexpressing CXCR4

  • 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.

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Author:Arezoo Jamali, Jamshid Hadjati, Zahra Madjd, Hamid Reza Mirzaei, Frederic Bastian ThalheimerORCiDGND, Shiwani Agarwal, Halvard-Björn BönigORCiDGND, Evelyn UllrichORCiDGND, Jessica HartmannORCiDGND
Parent Title (English):Frontiers in immunology
Publisher:Frontiers Media
Place of publication:Lausanne
Document Type:Article
Date of Publication (online):2020/08/28
Date of first Publication:2020/08/28
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2020/11/03
Tag:CAR; CD19; chemokine receptor 4; chimeric antigen receptor; fully human; huCAR19; immunotherapy; natural killer cell; transgenically augmented CAR NK cell
Issue:article 2028
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0