Department of Chemistry, University of Oslo, PO Box 1033 Blindern, NO-0315 Oslo, Norway.
Mol Immunol. 2011 Jul;48(12-13):1578-85. doi: 10.1016/j.molimm.2011.03.016. Epub 2011 May 18.
The EGF receptor is an important target of cancer immunotherapies. The 7A7 monoclonal antibody has been raised against the murine EGFR, but it cross-reacts with the human receptor. The results from experiments using immune-competent mice can therefore, in principle, be extrapolated to the corresponding scenario in humans. In this work we report the crystal structure of the 7A7 Fab at an effective resolution of 1.4Å. The antibody binding site comprises a deep pocket, located at the interface between the light and heavy chains, with major contributions from CDR loops H1, H2, H3 and L1. Binding experiments show that 7A7 recognizes a site on the EGFR extracellular domain that is not accessible in its most stable conformations, but that becomes exposed upon treatment with a tyrosine kinase inhibitor. This suggests a recognition mechanism similar to that proposed for mAb 806.
表皮生长因子受体是癌症免疫疗法的一个重要靶点。7A7 单克隆抗体是针对鼠 EGFR 产生的，但它与人类受体发生交叉反应。因此，使用免疫功能正常的小鼠进行的实验结果原则上可以外推到人类的相应情况。在这项工作中，我们报告了 7A7 Fab 的晶体结构，有效分辨率为 1.4Å。抗体结合位点包括一个位于轻链和重链之间界面的深口袋，主要由 CDR 环 H1、H2、H3 和 L1 贡献。结合实验表明，7A7 识别 EGFR 细胞外结构域上的一个位点，在其最稳定的构象中不可用，但在酪氨酸激酶抑制剂处理后会暴露出来。这表明其识别机制类似于 mAb 806 所提出的机制。
