Takahashi T, Yamaguchi T, Kitamura K, Noguchi A, Honda M
First Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Tohoku J Exp Med. 1992 Oct;168(2):371-4. doi: 10.1620/tjem.168.371.
Monoclonal antibody drug conjugate A7 was prepared from a mouse splenocyte immunized against human colon cancer. A7 reacted with 80 percent of colorectal cancer and pancreatic cancer. A7 was bound covalently to neocarzinostatin (NCS) to form A7-NCS. A7-NCS had strong cytotoxic activity in vivo and in vitro study. A total of 77 patients with colorectal cancer, including the patients with liver, lung and peritoneal metastasis, were treated with A7-NCS. There were some tumor reduction of liver metastasis on CT scan and pain relief. Follow up study of colorectal cancer patients treated with monoclonal antibody drug conjugate A7-NCS was carried out, with comparing to those treated conventional chemotherapy. Survival rate of the patients with postoperative liver metastasis treated with A7-NCS was slightly higher than that of the patients treated with conventional intraarterial infusion chemotherapy. There was no difference between the group treated with A7-NCS and that treated with conventional chemotherapy in the overall postoperative survival. Patients given a higher dose of the conjugate had a higher survival rate. There were no serious adverse effects in the patients given A7-NCS. Human anti-mouse antibody (HAMA) was detected in all A7-NCS treated patients.
单克隆抗体药物偶联物A7是由免疫人结肠癌的小鼠脾细胞制备而成。A7与80%的结直肠癌和胰腺癌发生反应。A7与新制癌菌素(NCS)共价结合形成A7-NCS。A7-NCS在体内和体外研究中均具有很强的细胞毒性活性。共有77例结直肠癌患者,包括有肝、肺和腹膜转移的患者,接受了A7-NCS治疗。CT扫描显示肝转移灶有一定程度缩小,且疼痛缓解。对接受单克隆抗体药物偶联物A7-NCS治疗的结直肠癌患者进行了随访研究,并与接受传统化疗的患者进行比较。接受A7-NCS治疗的术后肝转移患者的生存率略高于接受传统动脉内灌注化疗的患者。A7-NCS治疗组与传统化疗组在总体术后生存率方面无差异。给予较高剂量偶联物的患者生存率更高。接受A7-NCS治疗的患者未出现严重不良反应。在所有接受A7-NCS治疗的患者中均检测到了人抗鼠抗体(HAMA)。