Potent and specific killing of SLE donor B Cells with AlloNK^® (AB-101), an allogeneic cord blood-derived NK cell therapy, in combination with anti-CD19 or anti-CD20 monoclonal antibodies

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B845
Abstract ID: 5063

Presenting Author:
Paul Rogers , Principal Scientist at Artiva Biotherapeutics

Abstract:

B cells play a crucial role in the pathogenesis of SLE by producing autoantibodies that target self-antigens, leading to tissue damage and inflammation. Here we demonstrate proof of concept for the use of a NK cell therapy to enhance the depletion of SLE donor B cells in the presence of anti-CD19 or anti-CD20 antibodies by an antibody dependent cellular cytotoxicity (ADCC) mechanism. AlloNK^® is a non-engineered, allogeneic, off-the-shelf, cryopreserved NK cell product, currently being evaluated in a clinical trial in combination with rituximab in subjects with lupus nephritis. AlloNK, which has been optimized for ADCC, was tested in combination with anti-CD20 (rituximab, obinutuzumab) or anti-CD19 (tafasitamab) mAbs in a short-term ADCC assay to show specific killing of SLE donor B cells. PBMC were isolated from SLE donors and co-cultured with AlloNK at various effector to target (E:T) ratios and mAbs concentrations. After 4h, the percentage of caspase 3/7⁺ B and T cells was determined by flow cytometry. At a 1:1 E:T ratio, AlloNK mediated killing of B cells in the presence of obinutuzumab (range 79-95%), rituximab (range 19-62%), and tafasitamab (range 24-77%) in a dose-dependent manner. Killing was specific as no off-target apoptosis of T cells was observed. Taken together, these data suggest that AlloNK has the potential to be effective in combination with mAbs to induce deeper B cell depletion and improved efficacy, over the mAbs alone, in SLE.