Yamaguchi T, Tsurumi H, Kitamura K, Otsuji E, Miyagaki T, Kotani T, Takahashi T
First Department of Surgery, Kyoto Prefectural University of Medicine.
Jpn J Cancer Res. 1993 Nov;84(11):1190-4. doi: 10.1111/j.1349-7006.1993.tb02820.x.
A human/mouse chimeric Fab monoclonal antibody A7 (chFabA7) was covalently coupled to neocarzinostatin (NCS) by the SPDP method at various chFabA7:NCS substitution ratios. The antigen-binding activity of the conjugate, examined by ELISA using fixed antigen-positive colon cancer cells, was identical to that of the parent chFabA7 when one mole of NCS was conjugated, but was reduced with 2 or 3 moles of conjugated NCS. By means of a colony-forming assay, the cytocidal effect of the conjugate on antigen-positive cancer cells was found to be stronger than that of free NCS, whereas in antigen-negative cancer cells it was similar to that of free NCS. This effect was attenuated by adding an excess amount of monoclonal antibody A7. These findings indicate that the conjugate has an antigen-specific cytocidal action, and thus chFabA7-NCS is a promising tool for targeting cancer chemotherapy.
通过SPDP方法，以不同的人源/小鼠嵌合Fab单克隆抗体A7（chFabA7）与新制癌菌素（NCS）的取代比例，将人源/小鼠嵌合Fab单克隆抗体A7（chFabA7）与新制癌菌素（NCS）共价偶联。当一摩尔NCS偶联时，使用固定的抗原阳性结肠癌细胞通过ELISA检测的偶联物的抗原结合活性与亲本chFabA7相同，但当偶联2或3摩尔NCS时活性降低。通过集落形成试验，发现偶联物对抗原阳性癌细胞的杀细胞作用比游离NCS更强，而在抗原阴性癌细胞中，其作用与游离NCS相似。通过添加过量的单克隆抗体A7可减弱这种作用。这些发现表明偶联物具有抗原特异性杀细胞作用，因此chFabA7-NCS是一种有前景的靶向癌症化疗工具。
