Shih L B, Goldenberg D M, Xuan H, Lu H, Sharkey R M, Hall T C
Garden State Cancer Center, Newark, New Jersey.
Cancer Res. 1991 Aug 15;51(16):4192-8.
Anthracycline, either daunomycin or doxorubicin, was site specifically attached to the carbohydrate moiety of a monoclonal anticarcinoembryonic antigen antibody by using amino-dextran as the intermediate carrier. The reaction resulted in an immunoconjugate that contains approximately 20 to 25 molecules of drug per molecule of immunoglobulin G. Flow-cytometric studies revealed the retention of the antibody-binding activity. The immunoconjugate was cytotoxic to the target cells, as examined by the 75selenomethionine incorporation studies, and remained efficient for targeting a human colonic tumor (GW-39) in the nude mouse model. The conjugate possessed a greater antitumor activity against the subcutaneous tumor than either the free drug or an irrelevant antibody conjugate, and it was well tolerated by the animals at a much higher dose level than was the unconjugated drug.
通过使用氨基葡聚糖作为中间载体，将柔红霉素或阿霉素等蒽环类药物位点特异性地连接到单克隆抗癌胚抗原抗体的碳水化合物部分。该反应产生了一种免疫缀合物，每分子免疫球蛋白G含有约20至25个药物分子。流式细胞术研究显示抗体结合活性得以保留。通过75硒代蛋氨酸掺入研究检测，该免疫缀合物对靶细胞具有细胞毒性，并且在裸鼠模型中对人结肠肿瘤（GW-39）保持有效的靶向作用。与游离药物或无关抗体缀合物相比，该缀合物对皮下肿瘤具有更大的抗肿瘤活性，并且在比未缀合药物高得多的剂量水平下，动物对其耐受性良好。
