Hosono M, Endo K, Sakahara H, Watanabe Y, Saga T, Nakai T, Kawai C, Matsumori A, Yamada T, Watanabe T
Department of Nuclear Medicine, Kyoto University Hospital, Japan.
Br J Cancer. 1992 Feb;65(2):197-200. doi: 10.1038/bjc.1992.41.
Human anti-murine antibody (HAMA) response is a serious problem in the repeated infusion of murine monoclonal antibodies (MoAbs). HAMA positive sera were obtained from seven patients with colorectal cancer, pancreas cancer, malignant melanoma or myocardial infarction who had previously received radiolabelled MoAbs. The nature of HAMA was analysed using size exclusion high performance liquid chromatography (HPLC) after incubating with radiolabelled MoAbs including IgG, Fab or human/mouse chimeric Abs. Immune complexes composed of HAMA and MoAbs were formed. The percentage of radioactivity with a high molecular weight was related to HAMA levels determined by enzyme linked immunosorbent assay. Most radioactivity present in immune complex shifted to the antibody fraction after the addition of normal murine serum. All of seven sera were reactive with all four murine IgGs and this suggests that HAMA in these patients recognised the constant region of MoAbs. In one patient, HAMA was considered to recognise the variable region and to be anti-idiotypic. There was no significant binding with human/mouse chimeric Abs in any HAMA positive serum, although five out of seven patients were reactive with murine MoAb Fab, indicating that HAMA was composed of Abs responsive to the CH1 or CL region of murine IgG. These results suggest that (1) HAMA was composed of Ab responsive to Fc portion and/or CH1 or CL region of murine IgG, and (2) human/mouse chimeric Abs look promising in the repeated infusion of MoAb in HAMA positive patients.
人抗鼠抗体（HAMA）反应是重复输注鼠单克隆抗体（MoAb）时的一个严重问题。从7例曾接受放射性标记MoAb的结直肠癌、胰腺癌、恶性黑色素瘤或心肌梗死患者中获取HAMA阳性血清。在与包括IgG、Fab或人/鼠嵌合抗体在内的放射性标记MoAb孵育后，使用尺寸排阻高效液相色谱（HPLC）分析HAMA的性质。形成了由HAMA和MoAb组成的免疫复合物。高分子量放射性的百分比与酶联免疫吸附测定法测定的HAMA水平相关。加入正常鼠血清后，免疫复合物中存在的大部分放射性转移到抗体部分。所有7份血清均与所有4种鼠IgG反应，这表明这些患者中的HAMA识别MoAb的恒定区。在1例患者中，HAMA被认为识别可变区且为抗独特型。在任何HAMA阳性血清中，与人/鼠嵌合抗体均无明显结合，尽管7例患者中有5例与鼠MoAb Fab反应，表明HAMA由对鼠IgG的CH1或CL区有反应的抗体组成。这些结果表明：（1）HAMA由对鼠IgG的Fc部分和/或CH1或CL区有反应的抗体组成；（2）人/鼠嵌合抗体在HAMA阳性患者重复输注MoAb方面看起来很有前景。
