INVIVO ADMINISTRATION OF LYMPHOCYTE-SPECIFIC MONOCLONAL-ANTIBODIES IN NONHUMAN-PRIMATES - INVIVO STABILITY OF DISULFIDE-LINKED IMMUNOTOXIN CONJUGATES
INVIVO ADMINISTRATION OF LYMPHOCYTE-SPECIFIC MONOCLONAL-ANTIBODIES IN NONHUMAN-PRIMATES - INVIVO STABILITY OF DISULFIDE-LINKED IMMUNOTOXIN CONJUGATES
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DOI：
10.1172/jci112399
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发表时间：
1986-03-01
影响因子：
15.9
通讯作者：
LAMBERT, JM
中科院分区：
文献类型：
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作者：
LETVIN, NL;GOLDMACHER, VS;LAMBERT, JM
在恒河猴中评估免疫毒素的体内稳定性和循环清除率。所研究的免疫毒素是通过二硫键与核糖体失活毒素缀合的T细胞特异性单克隆抗T11抗体。单次静脉输注后，在猴循环中可检测到完整的免疫毒素。这是证明了定量流式细胞仪分析，凝胶过滤，和十二烷基硫酸钠凝胶电泳。在体外细胞毒性试验中，该完整偶联物在输注动物的血浆中显示出功能性。然而，许多因素导致循环免疫毒素水平低于最佳水平。当与核糖体失活毒素缀合时，抗体比天然抗体更快地被清除。此外，输注后，偶联物发生一些分解，导致产生可检测水平的循环游离抗体。目前的数据表明，使用免疫毒素作为治疗工具的人的可行性。
The stability in vivo and circulatory clearance of immunotoxins were assessed in rhesus monkeys. The immunotoxins studied were T cell-specific monoclonal anti-T11 antibodies conjugated by disulfide linkage to ribosome-inactivating toxins. Intact immunotoxin was detectable in the circulation of the monkeys following a single intravenous infusion. This was demonstrated by quantitative flow-cytometric analysis, gel-filtration, and sodium dodecyl sulfate-gel electrophoresis. This intact conjugate was shown to be functional in the plasma of the infused animals in an in vitro cytotoxicity assay. However, a number of factors contributed to bring the level of circulating immunotoxin to a less than optimal level. When conjugated to a ribosome-inactivating toxin, the antibody was cleared more rapidly than was the native antibody. Furthermore, following infusion, some breakdown of the conjugate occurred, resulting in the generation of detectable levels of circulating free antibody. The present data indicate the feasibility of using immunotoxins as therapeutic tools in man.