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抗尿轻链独特型抗体作为检测和破坏人类肿瘤性B淋巴细胞的试剂。

Antibodies against urinary light chain idiotypes as agents for detection and destruction of human neoplastic B lymphocytes.

作者信息

Tutt A L, Stevenson F K, Smith J L, Stevenson G T

出版信息

J Immunol. 1983 Dec;131(6):3058-63.

PMID:6417240
Abstract

Patients with B cell neoplasms frequently have low levels of tumor-related light chains in their urine; these light chains can be isolated with the use of relatively simple methods and then used to raise antibodies to the idiotypic determinants. In this study, anti-light chain idiotypes were raised against monoclonal light chains from the urine of four patients with chronic lymphocytic leukemia. The antibodies reacted specifically with the tumor cells of the homologous patient, assessed by immunofluorescence, and can therefore be used for tumor cell detection. In one case for which serum idiotypic IgM was available, the anti-light chain idiotype was shown to bind whole idiotypic IgM, and such binding could be inhibited by idiotypic IgM or idiotypic light chains, which demonstrates recognition of similar antigenic determinants. The binding of antibody to tumor cells was also totally inhibited by idiotypic IgM. The analysis of separated sera from the four patients for free light chains demonstrated only low levels (3.0 to 8.6 micrograms/ml of serum with a mean of 5.8), which suggests that light chain is rapidly cleared and therefore does not present a major barrier to antibody attack. It should be feasible to use such antibodies for both analysis and therapy of B cell neoplasms.

摘要

B细胞肿瘤患者的尿液中肿瘤相关轻链水平通常较低;这些轻链可以通过相对简单的方法分离出来,然后用于制备针对独特型决定簇的抗体。在本研究中,针对4例慢性淋巴细胞白血病患者尿液中的单克隆轻链制备了抗轻链独特型抗体。通过免疫荧光评估,这些抗体与同源患者的肿瘤细胞发生特异性反应,因此可用于肿瘤细胞检测。在1例可获得血清独特型IgM的病例中,抗轻链独特型抗体显示能结合完整的独特型IgM,且这种结合可被独特型IgM或独特型轻链抑制,这表明识别了相似的抗原决定簇。抗体与肿瘤细胞的结合也完全被独特型IgM抑制。对这4例患者分离血清中的游离轻链分析显示水平较低(血清中为3.0至8.6微克/毫升,平均为5.8),这表明轻链被迅速清除,因此不会对抗体攻击构成主要障碍。使用此类抗体进行B细胞肿瘤的分析和治疗应该是可行的。

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