Site-specific linkage of methotrexate to monoclonal antibodies using an intermediate carrier.
作者： Lisa Beewen Shih , Robert M. Sharkey , F. James Primus , David M. Goldenberg
关键词: Monoclonal 、 Carcinoembryonic antigen 、 Biochemistry 、 Flow cytometry 、 Immunoconjugate 、 Antigen 、 Antibody 、 Conjugate 、 Monoclonal antibody 、 Biology
摘要: The site-specific conjugation of methotrexate, 4-amino-N10-methylpteroylglutamic acid, to a monoclonal anti-carcinoembryonic antigen (CEA) antibody, using an intermediate amino-dextran carrier system, resulted in ratio 30-50 molecules MTX per molecule immunoglobulin. immunoreactivity the conjugate was analyzed flow cytometry or competitive binding assay, which showed that has significant retention antigen-binding activity. pharmacokinetic behavior immunoconjugate BALB/c mice and tumor localization hamsters indicated remained circulation with higher concentration than free could recognize as efficiently unconjugated antibody. high degree drug incorporation retained makes this method preferable direct antibody conjugation.
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