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

胰腺癌根治性切除术后复发是常见的，肝转移是影响预后的最重要因素。然后，我们尝试建立低副作用、高抗癌效果的术中化疗方案，研究了脂质体对胰腺癌细胞的靶向化疗。以阿霉素（ADM）作为抗癌剂进行包封，纯化的抗ca 19-9作为抗体进行偶联。体外采用我们建立的人胰腺癌细胞系PK-1，体内采用裸鼠皮下移植。在体外实验中，在ADM浓度分别为1、0.1和0.01 μ g/ml时，抗体偶联脂质体接触2 h后的生长抑制作用均强于游离ADM，特别是在0.01 μ g/ml时，只有抗体偶联脂质体与对照有显著差异。在体内，抗体偶联脂质体组ADM在肿瘤组织中的浓度最高，抑制生长的效果也最高。检测了脂质体在犬体内的分布。与游离ADM相比，ADM包封脂质体在肝脏内的蓄积超过3倍，但未出现明显的功能障碍。具体分布尚不清楚，但可能在肿瘤细胞附近长时间保留较高水平的ADM。因此，单克隆抗体结合脂质体的转运给药被认为是治疗性胰腺癌切除时防止肝转移的有效措施。

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.