Conjugated anti-TNF antibodies enhance the binding and degradation of TNF.

Biotechnology therapeutics Pub Date : 1992-01-01
V W Lee, M H Coan, C J Galloway
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引用次数: 0

Abstract

We have used disulfide-linked conjugates of murine anti-TNF antibodies to determine whether TNF binding to the cell surface could be increased by exploiting the Fc receptors present on monocytes and macrophages. Binding and degradation of TNF via Fc receptors may enhance the ability of anti-TNF antibodies to lower the high TNF levels found in several diseases. Conjugated murine anti-TNF antibodies greatly increased the binding of TNF to human U937 cells and had little effect on cells which did not express Fc receptors. U937 cells treated with anti-TNF conjugates also degraded more TNF than untreated cells. Competition analysis indicated that Fc receptors were involved in anti-TNF binding and that conjugated anti-TNF shared binding sites with monomeric anti-TNF. Preincubation of anti-TNF conjugates or monomeric anti-TNF with TNF increased the amount of anti-TNF antibody bound to the surface of cells. These results demonstrate that cross-linking may greatly enhance the ability of anti-TNF antibodies to mediate TNF clearance and degradation by making effective use of Fc receptors.

偶联抗TNF抗体增强TNF的结合和降解。
我们使用小鼠抗TNF抗体的二硫联偶联物来确定利用单核细胞和巨噬细胞上的Fc受体是否可以增加TNF与细胞表面的结合。通过Fc受体结合和降解TNF可能增强抗TNF抗体的能力,以降低在几种疾病中发现的高TNF水平。结合鼠抗TNF抗体可大大增加TNF与人U937细胞的结合,而对不表达Fc受体的细胞影响不大。用抗TNF偶联物处理的U937细胞也比未处理的细胞降解更多的TNF。竞争分析表明Fc受体参与了抗tnf的结合,并且偶联的抗tnf与单体抗tnf共享结合位点。抗TNF缀合物或单体抗TNF与TNF的预孵育增加了结合到细胞表面的抗TNF抗体的数量。这些结果表明,通过有效利用Fc受体,交联可以极大地增强抗TNF抗体介导TNF清除和降解的能力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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