Mining the human autoantibody repertoire: Isolation of potent IL17A-neutralizing monoclonal antibodies from a patient with thymoma |
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Authors: | Roger R Beerli Monika Bauer Andrea Fritzer Lindsey B Rosen Regula B Buser Markus Hanner Melanie Maudrich Mario Nebenfuehr Jorge Alejandro Sepulveda Toepfer Susanne Mangold Anton Bauer Steven M Holland Sarah K Browne Andreas Meinke |
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Institution: | 1.Valneva Austria GmbH; Campus Vienna Biocenter 3; Vienna, Austria;2.National Institute of Allergy and Infectious Diseases; Bethesda, MD USA;3.ImmunoQure Research AG, Schlieren, Switzerland;4.University of Zurich Hospital; Department of Dermatology; Zürich, Switzerland;5.Synlab; c/o Andreasklinik; Cham, Switzerland;6.NBE-Therapeutics LLC; Basel, Switzerland |
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Abstract: | Anti-cytokine autoantibodies have been widely reported to be present in human plasma, both in healthy subjects and in patients with underlying autoimmune conditions, such as autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) or thymic epithelial neoplasms. While often asymptomatic, they can cause or facilitate a wide range of diseases including opportunistic infections. The potential therapeutic value of specific neutralizing anti-cytokine autoantibodies has not been thoroughly investigated. Here we used mammalian cell display to isolate IL17A-specific antibodies from a thymoma patient with proven high-titer autoantibodies against the same. We identified 3 distinct clonotypes that efficiently neutralized IL17A in a cell-based in vitro assay. Their potencies were comparable to those of known neutralizing antibodies, including 2, AIN457 (secukinumab) and ixekizumab that are currently in clinical development for the treatment of various inflammatory disorders. These data clearly demonstrate that the human autoantibody repertoire can be mined for antibodies with high therapeutic potential for clinical development. |
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Keywords: | AIN457 human autoantibodies ixekizumab IL17 mammalian cell display monoclonal antibodies secukinumab Sindbis virus scFv-Fc |
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