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Bispecific Antibodies for Autoimmune and Inflammatory Diseases: Clinical Progress to Date

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Abstract

In autoimmune diseases, a highly complex network comprising diverse cytokines and their receptors on immune cells drives the inflammatory response. A number of therapeutic antibodies targeting these disease-related molecules have been approved for the treatment of autoimmune diseases. Bispecific antibodies (bsAbs), with binding specificity for two different target molecules, have recently been developed for a range of autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and psoriasis, and tested in clinical trials. This review briefly describes the three main categories of bsAb structures developed for autoimmune diseases, including immunoglobulin G (IgG)-like, natural IgG, and tandem antibody fragment formats. The bsAbs developed and evaluated to date mainly target the depletion of T or B cells, the inhibition of T cell differentiation or activation, or the neutralization of proinflammatory cytokines. The clinical evaluation of bsAbs in autoimmune diseases is ongoing, with both successes (phase II trials of obexelimab in systemic lupus erythematosus) and failures (phase II trials of lutikizumab in osteoarthritis and romilkimab in idiopathic pulmonary fibrosis), and this review aims to provide a comprehensive, up-to-date summary of the clinical progress of bsAbs in this therapeutic area. Although many challenges remain, bsAbs offer new therapeutic options in the future direction of autoimmune disease treatments.

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Acknowledgements

The author acknowledges support from The Science and Technology Development Fund, Macau SAR (File no. FDCT/131/2016/A3, FDCT/0015/2018/A1), the Multi-Year Research Grant (file no. MYRG2019-00069-FHS), Start-up Research Grant (file no.SRG2016-00082-FHS), the intramural research program of the Faculty of Health Sciences, University of Macau, and National Key Research and Development Project of the Ministry of Science and Technology of China (2019YFA09004400).

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  1. Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macau SPR, China

    Qi Zhao

  2. Cancer Centre, Faculty of Health Sciences, University of Macau, Taipa, Macau SPR, China

    Qi Zhao

  3. Biological Imaging and Stem Cell Core, Faculty of Health Sciences, University of Macau, Taipa, Macau SPR, China

    Qi Zhao

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Zhao, Q. Bispecific Antibodies for Autoimmune and Inflammatory Diseases: Clinical Progress to Date. BioDrugs 34, 111–119 (2020). https://doi.org/10.1007/s40259-019-00400-2

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