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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Homodimerization of tumor-reactive monoclonal antibodies markedly increases their ability to induce growth arrest or apoptosis of tumor cells
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Homodimerization of tumor-reactive monoclonal antibodies markedly increases their ability to induce growth arrest or apoptosis of tumor cells

机译：肿瘤反应性单克隆抗体的同质化显着提高了其诱导肿瘤细胞生长停滞或凋亡的能力

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摘要

Monoclonal antibodies (mAbs) that exert antitumor activity can do so by virtue of their effector function and/or their ability to signal growth arrest or cell death. In this study, we demonstrate that mAbs which have little or no signaling activity - i.e., anti-CD19, CD20, CD21, CD22 and Her-2 - can become potent antitumor agents when they are converted into IgG-IgG homodimers. The homodimers exert antigrowth activity by signaling G_0/G_1 arrest or apoptosis, depending upon which cell surface molecule they bind. This activity is specific and, in the case of the anti-CD19 mAb, did not require an Fc portion. These results offer the possibility that homodimers of other tumor-reactive mAbs which have little antitumor activity as monomers might be potent, anti- tumor agents.
机译：发挥抗肿瘤活性的单克隆抗体（mAb）可以凭借其效应子功能和/或发出信号来阻止生长或细胞死亡的能力来发挥作用。在这项研究中，我们证明了具有很少或没有信号传导活性的mAb，即抗CD19，CD20，CD21，CD22和Her-2，当它们转化为IgG-IgG同型二聚体时可以成为有效的抗肿瘤剂。同源二聚体通过发出信号G_0 / G_1停滞或凋亡来发挥抗生长活性，具体取决于它们结合的细胞表面分子。该活性是特异性的，并且在抗CD19 mAb的情况下，不需要Fc部分。这些结果提供了如下可能性：由于单体而几乎没有抗肿瘤活性的其他肿瘤反应性mAb的同二聚体可能是有效的抗肿瘤剂。

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