A tumor specific variant of the EGFR: Characterization and target for immunotherapy.

抗体是人体免疫系统的主要组成部分，它能结合（即粘附）外来物质，如病毒。一旦结合，这些抗体可以激活免疫系统的其他部分，帮助摧毁外来物质。与上述情况类似，许多机构正在测试与癌细胞结合的抗体，以确定它们是否能够摧毁这些细胞。这种治疗方法需要一种特异性结合癌细胞而非正常细胞的抗体。在这个提议中，我们希望测试一种新的抗体，它与细胞表面的一种叫做EGF受体的蛋白质结合。虽然在许多细胞表面都发现了EGF受体，但我们的抗体识别的是仅在癌细胞上发现的EGF受体的修饰版本。以往临床测试的EGF受体抗体都能识别正常的EGF受体，因此被证明是不合适的，因为它们与肝脏细胞结合会产生明显的副作用。预计我们的新抗体的特异性将克服这一问题。最终，这种抗体可用于治疗脑癌、乳腺癌、前列腺癌和肺癌患者。我们还将进行一些研究来确定这种修饰受体的功能。这项工作将提高我们对与肿瘤发展相关的事件的理解。

Antibodies are a major component of the bodies immune system that bind (i.e. stick) to foreign substances such as viruses. Once bound, these antibodies can activate other parts of the immune system, which help destroy the foreign substance. Analogous to the situation above, a number of institutions are testing antibodies that bind to cancer cells, in order to determine if they are able to destroy these cells. This therapeutic approach requires an antibody that specifically binds to cancer cells but not normal cells. In this proposal, we wish to test a novel antibody that binds to a protein on the cell surface called the EGF receptor. While the EGF receptor is found on the surface on many cells, our antibody recognizes a modified version of the EGF receptor that is found exclusively on cancer cells. Previous EGF receptor antibodies tested in the clinic all recognized the normal EGF receptor and thus proved unsuitable as they bound to cells in the liver causing significant side effects. It is anticipated that the specificity of our novel antibodies will overcome this problem. Eventually this antibody could be used to treat patients with brain, breast, prostate and lung cancer. We will also conduct a number of studies to determine the function of this modified receptor. This work will improve our understanding of those events associated with development of tumors.