P01
CAR-NK cell therapies for treatment of severe autoimmune diseases
M Arriens(1,2) A Eugster(4) E Bonifacio(4) S Bornstein(5) S Michen(6) A Temme(6) T Plötz(7) A Aigner(7) C Günther(8) K Hölig(1,2) S R Künzel(1,2) T Tonn(1,2,3) J Eitler(1,2,3)
1:Experimental Transfusion Medicine, Faculty of Medicine Carl Gustav Carus, Dresden University of Technology, Dresden; 2:Institute for Transfusion Medicine Dresden, German Red Cross Blood Donation Service North-East, Dresden, Germany; 3:German Cancer Consortium (DKTK), Partner Site Dresden, Dresden, Germany; 4:Center for Regenerative Therapies Dresden (CRTD), Dresden, Germany; 5:TU Dresden Department of Medicine III, University Hospital Carl Gustav Carus Dresden, Dresden, Germany; 6:Department of Neurosurgery, Section Experimental Neurosurgery/Tumor Immunology, University Hospital Carl Gustav Carus, TU Dresden, Germany; German Cancer Consortium (DKTK), Partner Site Dresden, Germany; National Center for Tumor Diseases (NCT/UCC), Dresden, Germany; 7:Rudolf-Boehm-Institute for Pharmacology and Toxicology, Clinical Pharmacology, Leipzig, Germany; Comprehensive Cancer Center Central Germany (CCCG), Site Leipzig, Leipzig, Germany; 8:Department of Dermatology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstrasse 74, Dresden, Dresden, Germany
Autoimmunity affects 8-10% of the world's population, and in many cases, the standard of care is expensive and non-curative. Recently, CD19-specific chimeric antigen receptor (CAR) T cells have shown encouraging clinical efficacy in the treatment of selected B-cell-driven autoimmune diseases. However, autologous CAR-T cell therapy is expensive, logistically complex and has been associated with potentially serious side effects in the treatment of hematologic malignancies. Alternatively, natural killer (NK) cells have been shown to be potent but safe cytotoxic cells in hematologic oncology settings and can be used allogeneically as an off-the-shelf product.
Here, we developed CAR-NK cells targeting autoimmunity. We lentivirally transduced the clinically used NK-92 NK cell line or peripheral blood-isolated primary NK cells with a CAR targeting the pan-B cell CD19 molecule (CD19.CAR) or with a CAR specifically binding B cells that are autoreactive against the DSG3 protein (DSG3.CAR).
CD19.CAR NK-92 and CD19.CAR primary NK cells showed stable CAR expression and high cytotoxicity against the CD19-positive B cell line NALM-6. In addition, CD19.CAR NK-92 cells selectively depleted B cells from autoimmune patients in vitro, while leaving other cell populations unaffected. DSG3.CAR NK-92 cells also exhibited strong and stable CAR expression and demonstrated functionality in a CD107a-based degranulation assay after stimulation with immobilized anti-DSG3 antibodies.
Thus, our data demonstrate that CAR-NK cells can selectively eliminate B cells and have a great potential for curative, affordable and safe treatment of patients with B cell-driven autoimmune diseases.