A Novel Fusion Protein, AChR-Fc, Ameliorates Myasthenia Gravis by Neutralizing Antiacetylcholine Receptor Antibodies and Suppressing Acetylcholine Receptor-Reactive B Cells.
Most patients with myasthenia gravis (MG) have elevated levels of autoantibodies against the nicotinic acetylcholine receptor (AChR) at the neuromuscular junction, which leads to muscle weakness. We developed a fusion protein, AChR-Fc, as a novel therapeutic biomolecule for patients with MG and examined its efficacy. AChR-Fc was expressed by Chinese hamster ovary cells and purified. We examined the neutralizing activity and cellular cytotoxicity of AChR-Fc using anti-AChR antibody-producing hybridoma cells and serum samples from 16 patients with MG. The effects of AChR-Fc in vivo were also examined using rat MG models. AChR-Fc bound to anti-AChR antibodies and exhibited cytotoxicity against patient-derived antibody-producing B cells. Additionally, a dose-dependent improvement in the clinical signs of disease was observed in a rat MG model. AChR-Fc can diminish signs of MG by neutralizing anti-AChR antibodies and enhancing cytotoxicity against autoantibody-producing B cells. Thus, AChR-Fc can be a novel therapeutic biomolecule for patients with MG.
Research Laboratory, Nihon Pharmaceutical Co. Ltd., Chiba, Japan. homma@nihon-pharm.co.jp.
Masayuki
M
Homma
Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Akiyuki
A
Uzawa
Research Laboratory, Nihon Pharmaceutical Co. Ltd., Chiba, Japan.
Hitoshi
H
Tanaka
Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Naoki
N
Kawaguchi
Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Tetsuya
T
Kanai
Research Laboratory, Nihon Pharmaceutical Co. Ltd., Chiba, Japan.
Kenji
K
Nakajima
Research Laboratory, Nihon Pharmaceutical Co. Ltd., Chiba, Japan.
Masakuni
M
Narita
Research Laboratory, Nihon Pharmaceutical Co. Ltd., Chiba, Japan.
Yukio
Y
Hara
Research Laboratory, Nihon Pharmaceutical Co. Ltd., Chiba, Japan.
Hideya
H
Maruyama
Research Laboratory, Nihon Pharmaceutical Co. Ltd., Chiba, Japan.
Yasumasa
Y
Ogawa
Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Keiichi
K
Himuro
Department of Neurology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Satoshi
S
Kuwabara
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001323:Autoantibodies / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D006224:Cricetinae; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000276:immunology*; D051381:Rats; D011978:Receptors, Nicotinic / Q000276:immunology* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D014611:Vaccination; D055815:Young Adult
D001323:Autoantibodies; D011978:Receptors, Nicotinic; D011993:Recombinant Fusion Proteins
AChR-Fc; ADCC; Anti-AChR antibody; Myasthenia gravis; Neutralization
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