La/SSB chimeric autoantibody receptor modified NK92MI cells for targeted therapy of autoimmune disease

• Published in: Clinical immunology (Orlando, Fla.) Fla.), 2018-07, Vol.192, p.40-49
• Main Authors: Meng, Huimin, Sun, Xue, Song, Yanhui, Zou, Jianxuan, An, Gangli, Jin, Zeming, Yang, Lin
• Format: Article
• Language: English
• Subjects: Autoantibodies; Autoantibodies - immunology; Autoantigens - immunology; Autoimmune diseases; Autoimmune Diseases - immunology; Autoimmune Diseases - therapy; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; Cell Line, Tumor; Chimeric autoantibody receptor; Epitopes - immunology; HEK293 Cells; Humans; Immunotherapy, Adoptive - methods; Jurkat Cells; La/SSB; NK92MI cells; Peptide Fragments - immunology; Receptors, Antigen, B-Cell - immunology; Receptors, Antigen, B-Cell - metabolism; Receptors, Chimeric Antigen - immunology; Receptors, Chimeric Antigen - metabolism
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1016/j.clim.2018.04.006

It has been long sought to specifically eliminate B-cell clones that generate autoreactive antibodies, while sparing the immune system when combating autoimmune disease. Although it was impossible to achieve this goal before, newly developed techniques have made it feasible today. Autoantibodies against La/SSB were involved in several autoimmune diseases. Here, we aimed to introduce La/SSB epitope-based chimeric autoantibody receptors (CAAR) into NK92MI cells enabled it to destroy the corresponding La/SSB-specific B cell receptor (BCR) -bearing lymphoma cells (LaA-BCR-Romas, LaA-BCR-Maver-1, and LaA-BCR-Jurkat cells). Such cell lines could eliminate a part of the B-cells in the blood of patients positive for anti-La/SSB antibodies. The CAAR we used in this study was constructed by fusing fragments from the nucleus protein, La/SSB, with the TCR signaling molecules, CD28, CD137, and CD3ζ. Thus, this method could specifically destroy the La/SSB autoreactive B-cell clones. Our results might provide a new strategy to combat antibody-mediated autoimmune diseases. •Develop a novel therapeutic option for autoimmune disease.•Generate a novel CAAR modified NK92MI cell line which can selectively target autoreactive B-cells.•CAAR NK92MI cell line can destroy a part of the B-cells in the blood of patients and potentially to be used in clinical trials.