Shih L B, Xuan H, Sharkey R M, Goldenberg D M
Center for Molecular Medicine and Immunology, UMDNJ, Newark 07103.
Int J Cancer. 1990 Dec 15;46(6):1101-6. doi: 10.1002/ijc.2910460625.
5-fluorouridine (FUR), an antineoplastic agent, was site-specifically conjugated to the carbohydrate moiety of a anticarcinoembryonic antigen (CEA) monoclonal antibody (MAb) by using amino-dextran as the intermediate carrier. The final immunoconjugate contains approximately 30-35 molecules of FUR per molecule of immunoglobulin, has immunoreactivity retained as examined by flow cytometry, and is cytotoxic to the target cells as examined by 75selenomethionine incorporation studies. In the GW-39/nude mouse model, the conjugate remained efficient in targeting the human colonic tumor and possessed greater inhibitory growth effects on the subcutaneous tumor than free FUR or an irrelevant antibody conjugate. In addition, the reduced host toxicity of the conjugate may permit the use of this agent in a high-dose therapy of this tumor system.
5-氟尿苷（FUR）是一种抗肿瘤药物，通过使用氨基葡聚糖作为中间载体，将其位点特异性地偶联到抗癌胚抗原（CEA）单克隆抗体（MAb）的碳水化合物部分。最终的免疫偶联物每分子免疫球蛋白含有约30-35个FUR分子，通过流式细胞术检测保留了免疫反应性，并且通过75硒蛋氨酸掺入研究检测对靶细胞具有细胞毒性。在GW-39/裸鼠模型中，该偶联物在靶向人结肠肿瘤方面仍然有效，并且对皮下肿瘤的生长抑制作用比游离FUR或无关抗体偶联物更大。此外，该偶联物降低的宿主毒性可能允许在该肿瘤系统的高剂量治疗中使用该药物。
