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Analysis of nonhuman N-glycans as the minor constituents in recombinant monoclonal antibody pharmaceuticals.
Maeda, Eiki; Kita, Soichiro; Kinoshita, Mitsuhiro; Urakami, Koji; Hayakawa, Takao; Kakehi, Kazuaki.
Afiliação
  • Maeda E; Analytical Development Laboratories, CMC Center, Takeda Pharmaceutical Company Limited, Jusohonmachi 2-17-85, Yodogawa-ku, Osaka 532-8686, Japan.
Anal Chem ; 84(5): 2373-9, 2012 Mar 06.
Article em En | MEDLINE | ID: mdl-22394092
Minor N-linked glycans containing N-glycolylneuraminic acid residues and/or α-Gal epitopes (i.e., galactose-α1,3-galactose residues) have been reported to be present in recombinant monoclonal antibody (mAb) therapeutics. These contaminations are due to their production processes using nonhuman mammalian cell lines in culture media containing animal-derived materials. In case of the treatment of tumors, we inevitably use such mAbs by careful risk-benefit considerations to prolong patients' lives. However, expanding their clinical applications such as for rheumatism, asthma, and analgesia demands more careful evaluation of the product characteristics. The present work for detailed evaluations of N-glycans demonstrates the methods using capillary electrophoresis with laser-induced fluorescence detection (CE-LIF) and a combination of high-performance liquid chromatography and electrospray ionization time-of-flight mass spectrometry. The CE-LIF method provides excellent separation of both major and minor N-glycans from six commercial mAb pharmaceuticals within 30 min and clearly indicates that a possible trigger of immunogenicity in humans due to the presence of nonhuman N-glycans is present. We strongly believe that the proposed method will be a powerful tool for the analysis of N-glycans of recombinant mAb products in various development stages, such as clone selection, process control, and routine release testing to ensure safety and efficacy of the products.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Polissacarídeos / Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz / Eletroforese Capilar / Espectrometria de Massas por Ionização por Electrospray / Anticorpos Monoclonais Idioma: En Ano de publicação: 2012 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Polissacarídeos / Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz / Eletroforese Capilar / Espectrometria de Massas por Ionização por Electrospray / Anticorpos Monoclonais Idioma: En Ano de publicação: 2012 Tipo de documento: Article