THE STUDY OF TARGETING CHEMOTHERAPY USING ANTIBODY-CONJUGATED LIPOSOME AGAINST PANCREATIC CANCER

胰腺癌根治性切除术后复发率高，肝转移是影响预后的重要因素。为了建立一种低毒副作用、高抗癌效果的术中化疗方法，我们研究了脂质体靶向治疗胰腺癌细胞的方法。阿霉素（ADM）作为抗癌剂被封装，纯化的抗CA 19-9作为抗体被偶联。体外实验采用我们建立的人胰腺癌细胞株PK-1，体内实验采用其裸鼠皮下移植瘤。在体外实验中，在1、0.1和0.01 μ g/ml的ADM浓度下，抗体结合的脂质体在接触两小时后显示出比游离ADM更强的生长抑制作用，尤其是在0.01 μ g/ml时，只有抗体结合的脂质体显示出与对照组的显著差异。在体内实验中，抗体结合脂质体组肿瘤组织中ADM浓度最高，抑瘤效果最好。在犬体内考察脂质体的分布。与游离ADM相比，ADM脂质体在肝脏中的蓄积量增加了3倍以上，但未出现明显的功能障碍。详细的分布尚不清楚，但较高水平的ADM在肿瘤细胞附近较长时间的保留是可能的。因此，单克隆抗体缀合的脂质体的经皮给药被认为是在胰腺癌的治愈性切除的情况下对抗肝转移的有效措施。

Post-operative recurrence is frequent in cases of curative resection of pancreatic cancer, and liver metastasis is the most important factor for prognosis. Then, attempting to establish intraoperative chemotherapy with lower side-effect and higher anti-cancer effect, we have studied the targeting chemotherapy using liposome against pancreatic cancer cells. Adriamycin (ADM) was used as anti-cancer agent to be encapsulated, and purified-anti-CA 19-9 as an antibody to be conjugated. In vitro, the human pancreatic cancer cell line, PK-1, established by us, and in vivo, its subcutaneous graft to nude mice were used. In vitro, at each concentration of 1, 0.1 and 0.01 mu g/ml of ADM, the antibody-conjugated liposome showed a stronger growth-inhibitory effect after two hours contact than free ADM, and especially at 0.01 mu g/ml, only the antibody-conjugated liposome showed a significant difference from the control. In vivo, in group of antibody-conjugated liposome the highest concentration of ADM in tumor tissue and the highest growth inhibitory effect were obtained. The distribution of liposome was examined on dogs. As compared with free ADM, ADM-encapsulated liposome showed over three times accumulation in the liver without accompanying any significant dysfunction. The detailed distribution is not clear, but longer retention of a higher level of ADM near tumor cells is probable Accordingly, the transportal administration of mono- clonal antibody-conjugated liposome is considered to be an effective measure against liver metastasis in cases of curative resection of pancreatic cancer.