Kobayashi H, Sakahara H, Saga T, Hosono M, Shirato M, Kanda H, Ishibashi K, Watanabe T, Endo K, Ishiwata I
Department of Nuclear Medicine, Kyoto University Faculty of Medicine, Japan.
Cancer Immunol Immunother. 1993 Aug;37(3):143-9. doi: 10.1007/BF01525427.
Murine monoclonal antibody 196-14 recognizes the ovarian-cancer-associated antigen CA125, but the epitope it recognizes is different from that of monoclonal antibody OC125. We developed a human/mouse chimeric 196-14 using the variable regions of the murine 196-14 and human heavy-chain (gamma 1) and light-chain (kappa) constant regions. Cell binding and competitive inhibition assays using chimeric 196-14 labeled with 125I, 111In or 99mTc demonstrated that the in vitro immunoreactivity of the chimeric antibody was identical to that of the parental murine monoclonal antibody. However, in mice bearing human ovarian cancer xenografts, the clearance from blood was faster and absolute levels of accumulation in the tumor were lower for the 125I-labeled or 99mTc-labeled chimeric antibody than for the murine antibody labeled with the corresponding radionuclides. The tumor-to-blood radioactivity ratio was not significantly different between the chimeric antibody and the murine antibody, regardless of the radionuclide used for labeling. Chimeric antibody 196-14 labeled with 131I, 111In or 99mTc is promising for the radioimmunoimaging of ovarian cancer.
鼠单克隆抗体196 - 14可识别卵巢癌相关抗原CA125，但其识别的表位与单克隆抗体OC125不同。我们利用鼠196 - 14的可变区以及人重链（γ1）和轻链（κ）恒定区构建了人/鼠嵌合抗体196 - 14。使用用125I、111In或99mTc标记的嵌合抗体196 - 14进行细胞结合和竞争抑制试验表明，该嵌合抗体的体外免疫反应性与亲本鼠单克隆抗体相同。然而，在携带人卵巢癌异种移植瘤的小鼠中，与用相应放射性核素标记的鼠抗体相比，125I标记或99mTc标记的嵌合抗体从血液中的清除更快，在肿瘤中的绝对积累水平更低。无论用于标记的放射性核素如何，嵌合抗体与鼠抗体之间的肿瘤与血液放射性比值均无显著差异。用131I、111In或99mTc标记的嵌合抗体196 - 14在卵巢癌放射免疫显像方面具有应用前景。
