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Mining the human autoantibody repertoire: isolation of potent IL17A-neutralizing
monoclonal antibodies from a patient with thymoma
#MMPMID25484038
Beerli RR
; Bauer M
; Fritzer A
; Rosen LB
; Buser RB
; Hanner M
; Maudrich M
; Nebenfuehr M
; Toepfer JA
; Mangold S
; Bauer A
; Holland SM
; Browne SK
; Meinke A
MAbs
2014[]; 6
(6
): 1608-20
PMID25484038
show ga
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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