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Anti‐murine Antibody Response to Mouse Monoclonal Antibodies in Cancer Patients

机译:癌症患者对小鼠单克隆抗体的抗鼠抗体反应

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摘要

Although development of human anti‐murine inununoglobulin antibody (HAMA) is often seen in patients receiving murine antibodies, the variety of methods used for detecting HAMA makes it difficult to compare directly the HAMA responses measured by different assays. In the present study, several parameters of the HAMA response to two murine monoclonal antibodies were evaluated. The anti‐sialosyl Tn antibody MLS102 and anti‐CA125 antibody 145‐9, which were labeled with 111ln, were injected intravenously into 17 colorectal cancer patients and 11 ovarian cancer patients for immnnoscintigraphy, respectively. HAMA was measured by enzyme‐linked immunosorbent assay. There was no difference in baseline HAMA levels before antibody injection between the two groups. HAMA developed more frequently in ovarian cancer patients receiving the 145‐9 antibody than in colorectal cancer patients receiving the MLS102 antibody (9/11 vs. 6/17, P<0.05). No significant difference was observed in maximal HAMA levels between the two groups of patients. However, time to reach the maximal levels was delayed and the duration of the response seemed longer in ovarian cancer patients. Among 11 patients receiving the 145‐9 antibody three patients became positive for HAMA more than 2 months after antibody injection and the other two had HAMA activity in their sera for more than 17 months. HAMA response was different between the two antibodies, and late onset or long duration of HAMA response against the 145‐9 antibody suggests the importance of HAMA measurement in patients who receive a second injection of murine antibodies even after a long interval.
机译:尽管在接受鼠源抗体的患者中经常会看到人类抗鼠类免疫球蛋白抗体(HAMA)的发展,但是用于检测HAMA的方法多种多样,使得难以直接比较通过不同检测方法测得的HAMA反应。在本研究中,评估了对两种鼠类单克隆抗体的HAMA反应的几个参数。将分别标记为 111 ln的抗唾液酸Tn抗体MLS102和抗CA125抗体145-9分别静脉注射到17例结直肠癌患者和11例卵巢癌患者中以进行免疫闪烁显像。通过酶联免疫吸附测定法测量HAMA。两组之间的抗体注射前基线HAMA水平无差异。与接受MLS102抗体的大肠癌患者相比,接受145-9抗体的卵巢癌患者中HAMA的发生频率更高(9/11与6/17,P <0.05)。两组患者之间的最大HAMA水平没有观察到显着差异。但是,卵巢癌患者达到最高水平的时间被延迟,反应时间似乎更长。在接受145-9抗体的11例患者中,有3例患者在抗体注射后2个月以上就对HAMA呈阳性,另外2例患者的血清中有HAMA活性超过17个月。两种抗体之间的HAMA反应有所不同,并且针对145-9抗体的HAMA反应起效较晚或持续时间较长,这表明即使在很长的间隔后再次接受鼠抗体注射的患者,HAMA测量的重要性。

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