Shih L B, Sharkey R M, Primus F J, Goldenberg D M
Center for Molecular Medicine and Immunology, University of Medicine and Dentistry of New Jersey, Newark 07103.
Int J Cancer. 1988 Jun 15;41(6):832-9. doi: 10.1002/ijc.2910410610.
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 a ratio of 30-50 molecules of MTX per molecule of immunoglobulin. The immunoreactivity of the conjugate was analyzed using flow cytometry or a competitive binding assay, which showed that the conjugate has significant retention of the antigen-binding activity. The pharmacokinetic behavior of the immunoconjugate in BALB/c mice and tumor localization in hamsters indicated that the conjugate remained in the circulation with higher concentration than free antibody, and could recognize the tumor as efficiently as the unconjugated antibody. The high degree of drug incorporation with retained immunoreactivity makes this method preferable to direct antibody conjugation.
使用中间氨基葡聚糖载体系统，将甲氨蝶呤（4-氨基-N10-甲基蝶酰谷氨酸）位点特异性缀合至单克隆抗癌胚抗原（CEA）抗体上，得到每分子免疫球蛋白含有30至50个甲氨蝶呤分子的比例。使用流式细胞术或竞争性结合试验分析缀合物的免疫反应性，结果表明该缀合物显著保留了抗原结合活性。免疫缀合物在BALB/c小鼠中的药代动力学行为以及在仓鼠中的肿瘤定位表明，该缀合物在循环中的浓度高于游离抗体，并且能够与未缀合的抗体一样有效地识别肿瘤。药物掺入程度高且保留免疫反应性使得该方法优于直接抗体缀合。
