新制癌菌素与Fab人/鼠嵌合单克隆抗体A7联合应用对人结直肠癌的体内疗效
In vivo efficacy of neocarzinostatin coupled with Fab human/mouse chimeric monoclonal antibody A7 against human colorectal cancer.
作者信息
Yamaguchi T, Tsurumi H, Kotani T, Yamaoka N, Otsuji E, Kitamura K, Takahashi T
机构信息
First Department of Surgery, Kyoto Prefectural University of Medicine, Kyoto.
出版信息
Jpn J Cancer Res. 1994 Feb;85(2):167-71. doi: 10.1111/j.1349-7006.1994.tb02078.x.
The anticancer polypeptide neocarzinostatin (NCS) was covalently coupled to a human/mouse chimeric Fab A7 monoclonal antibody (chFabA7) and the in vivo efficacy of this conjugate was examined. NCS concentration assay was carried out, and acute toxicity and tumoricidal effects were examined. The concentration assay, using anti-NCS monoclonal antibody, revealed that administration of the chA7Fab conjugate leads to a greater blood retention and a higher tumor accumulation of NCS, when compared to free NCS administration. The tumoricidal effect of chA7Fab-NCS was higher than that of either free NCS or the saline control, against antigen-positive tumors. In antigen-negative tumors there was no difference in toxic effect among the three preparations. Values of LD50, reflecting acute toxicity, were 5050 U/kg and 3600 U/kg for the chA7Fab-NCS and the free NCS, respectively. These results suggest that chFabA7-NCS may be a promising tool for targeting cancer chemotherapy.
将抗癌多肽新制癌菌素（NCS）与一种人/鼠嵌合Fab A7单克隆抗体（chFabA7）共价偶联，并检测了该偶联物的体内疗效。进行了NCS浓度测定，并检测了急性毒性和杀肿瘤效果。使用抗NCS单克隆抗体进行的浓度测定表明，与游离NCS给药相比，chA7Fab偶联物的给药导致NCS在血液中的保留时间更长，在肿瘤中的积累更高。chA7Fab-NCS对抗抗原阳性肿瘤的杀肿瘤效果高于游离NCS或生理盐水对照。在抗原阴性肿瘤中，三种制剂的毒性作用没有差异。反映急性毒性的LD50值，chA7Fab-NCS和游离NCS分别为5050 U/kg和3600 U/kg。这些结果表明，chFabA7-NCS可能是一种有前途的靶向癌症化疗工具。
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