Masuda K, Nagata S, Hirano K, Takagishi Y, Hirai H
Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
Biochim Biophys Acta. 1993 Sep 8;1182(2):128-32. doi: 10.1016/0925-4439(93)90132-k.
This study was carried out to clarify the reason for elevation of serum alpha-fetoprotein (AFP) level of nude mice bearing hepatoma cells after treatment with monoclonal antibodies (MoAbs) to AFP. MoAbs to AFP showed no effect on the cumulative amounts of AFP secreted from human hepatoma cell line, HuH-7, in vitro. However, the treatment of nude mice bearing HuH-7N cells (HuH-7 xenograft) with MoAbs to AFP led to elevation of the serum AFP level in spite of the fact that the growth curve of HuH-7N cells was similar to that for PBS treatment. This apparent elevation of the serum AFP level is thought to be due to the slow elimination of AFP-MoAb immune complexes with little lattice structure from circulation, but not the enhancement of AFP secretion of HuH-7N cells. Thus, when using a MoAb alone or MoAb-drug conjugate, the serum AFP level should only be cautiously used as a tumor marker for evaluating the targeting immunotherapy.
本研究旨在阐明用抗甲胎蛋白(AFP)单克隆抗体(MoAbs)治疗后,荷肝癌细胞裸鼠血清甲胎蛋白(AFP)水平升高的原因。抗AFP的MoAbs对人肝癌细胞系HuH-7体外分泌AFP的累积量无影响。然而,用抗AFP的MoAbs治疗荷HuH-7N细胞(HuH-7异种移植)的裸鼠,尽管HuH-7N细胞的生长曲线与用磷酸盐缓冲盐水(PBS)处理的相似,但血清AFP水平仍升高。血清AFP水平的这种明显升高被认为是由于循环中晶格结构少的AFP-MoAb免疫复合物清除缓慢,而非HuH-7N细胞AFP分泌增加所致。因此,单独使用MoAb或MoAb-药物偶联物时,血清AFP水平仅应谨慎用作评估靶向免疫治疗的肿瘤标志物。