A HUMAN MOUSE CHIMERIC MONOCLONAL-ANTIBODY AGAINST CA-125 FOR RADIOIMMUNOIMAGING OF OVARIAN-CANCER
A HUMAN MOUSE CHIMERIC MONOCLONAL-ANTIBODY AGAINST CA-125 FOR RADIOIMMUNOIMAGING OF OVARIAN-CANCER
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DOI：
10.1007/bf01525427
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发表时间：
1993-08-01
影响因子：
5.8
通讯作者：
KONISHI, J
中科院分区：
文献类型：
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作者：
KOBAYASHI, H;SAKAHARA, H;KONISHI, J
鼠单克隆抗体196-14识别卵巢癌相关抗原CA 125，但它识别的表位与单克隆抗体OC 125的表位不同。我们使用鼠196- 14的可变区和人重链（γ 1）和轻链（κ）恒定区开发了人/小鼠嵌合体196-14。使用I-125、In-111或Tc-99 m标记的嵌合196-14进行的细胞结合和竞争性抑制试验证明，嵌合抗体的体外免疫反应性与亲本鼠单克隆抗体的免疫反应性相同。然而，在携带人卵巢癌异种移植物的小鼠中，与用相应放射性核素标记的鼠抗体相比，I-125标记或Tc-99 m标记的嵌合抗体从血液中的清除更快，并且在肿瘤中累积的绝对水平更低。无论用于标记的放射性核素如何，嵌合抗体和鼠抗体之间的肿瘤与血液放射性比率没有显著差异。嵌合抗体196-14经I-131、In-111或Tc-99 m标记后，可望用于卵巢癌的放射免疫显像。
Murine monoclonal antibody 196-14 recognizes the ovarian-cancer-associated antigen CA125, but the epitope it recognizes is different from that of monoclonal antibody OC 125. We developed a human/mouse chimeric 196-14 using the variable regions of the murine 196-14 and human heavy-chain (gamma1) and light-chain (kappa) constant regions. Cell binding and competitive inhibition assays using chimeric 196-14 labeled with I-125, In-111 or Tc-99m 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 I-125-labeled or Tc-99m-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 I-131, In-111 or Tc-99m is promising for the radioimmunoimaging of ovarian cancer.