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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Synergistic down-regulation of receptor tyrosine kinases by combinations of mAbs: implications for cancer immunotherapy.
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Synergistic down-regulation of receptor tyrosine kinases by combinations of mAbs: implications for cancer immunotherapy.

机译：单克隆抗体的组合对受体酪氨酸激酶的协同下调：对癌症免疫治疗的意义。

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摘要

mAbs to receptor tyrosine kinases such as EGF receptor/ErbB-1 and HER2/ErbB-2 inhibit the tumorigenic growth of certain cancer cells, but although recombinant versions of such Abs are already used in oncology wards, the mechanism underlying immunotherapy remains unknown. We report that anti-EGF receptor Abs promote a slow endocytic process distinct from the rapid EGF-induced receptor internalization. Combining mAbs that engage distinct epitopes significantly accelerates receptor degradation. In addition, mAb combinations are more effective than single Abs in inhibiting HER2 signaling in vitro and tumorigenesis in animals. We present a model attributing efficacy of immunotherapy to the size of Ab-receptor lattices formed at the cell surface, which dictates the rate of endocytic clearance and extent of signaling blockade.
机译：受体酪氨酸激酶（例如EGF受体/ ErbB-1和HER2 / ErbB-2）的单克隆抗体抑制某些癌细胞的致瘤性生长，但是尽管此类Ab的重组形式已用于肿瘤病房，但免疫疗法的基本机制仍然未知。我们报道抗EGF受体Abs促进一个缓慢的内吞过程不同于快速EGF诱导受体内在化。结合不同表位的mAb显着加速受体降解。另外，mAb组合在体外抑制HER2信号转导和动物肿瘤发生方面比单一Abs更有效。我们提出了一种将免疫疗法的功效归因于在细胞表面形成的Ab受体晶格大小的模型，该模型决定了胞吞清除的速率和信号传导阻断的程度。

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