Mining the human autoantibody repertoire: Isolation of potent IL17A-neutralizing monoclonal antibodies from a patient with thymoma

作者：Beerli Roger R; Bauer Monika; Fritzer Andrea; Rosen Lindsey B; Buser Regula B; Hanner Markus; Maudrich Melanie; Nebenfuehr Mario; Toepfer Jorge Alejandro Sepulveda; Mangold Susanne; Bauer Anton; Holland Steven M; Browne Sarah K; Meinke Andreas^*

来源：mAbs, 2014, 6(6): 1608-1620.

DOI：10.4161/mabs.36292

• AIN457
• human autoantibodies
• ixekizumab
• IL17
• mammalian cell display
• monoclonal antibodies
• secukinumab
• Sindbis virus
• scFv-Fc

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 anticytokine 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.

• 出版日期2014-12