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首页> 外文期刊>Journal of Molecular Biology >Internalizing cancer antibodies from phage libraries selected on tumor cells and yeast-displayed tumor antigens.
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Internalizing cancer antibodies from phage libraries selected on tumor cells and yeast-displayed tumor antigens.

机译：从在肿瘤细胞和酵母菌展示的肿瘤抗原中选择的噬菌体库内化癌症抗体。

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摘要

A number of approaches have been utilized to generate antibodies to cancer cell surface receptors that can be used as potential therapeutics. A number of these therapeutic approaches, including antibody-drug conjugates, immunotoxins, and targeted nucleic acid delivery, require antibodies that not only bind receptor but also undergo internalization into the cell upon binding. We previously reported on the ability to generate cancer cell binding and internalizing antibodies directly from human phage antibody libraries selected for internalization into cancer cell lines. While a number of useful antibodies have been generated using this approach, limitations include the inability to direct the selections to specific antigens and to identify the antigen bound by the antibodies. Here we show that these limitations can be overcome by using yeast-displayed antigens known to be associated with a cell type to select the phage antibody output after several rounds of selection on a mammalian cell line. We used this approach to generate several human phage antibodies to yeast-displayed EphA2 and CD44. The antibodies bound both yeast-displayed and mammalian cell surface antigens, and were endocytosed upon binding to mammalian cells. This approach is generalizable to many mammalian cell surface proteins, results in the generation of functional internalizing antibodies, and does not require antigen expression and purification for antibody generation.
机译：已经采用了许多方法来产生针对癌细胞表面受体的抗体，这些抗体可以用作潜在的治疗方法。这些治疗方法中的许多方法，包括抗体-药物偶联物，免疫毒素和靶向核酸的传递，都需要不仅结合受体而且结合后也被内在化的抗体。我们先前曾报道过直接从选择用于内化成癌细胞系的人噬菌体抗体库中产生癌细胞结合和内化抗体的能力。尽管使用这种方法已经产生了许多有用的抗体，但局限性包括无法将选择引导至特定抗原，也无法鉴定与抗体结合的抗原。在这里，我们显示可以通过使用已知与细胞类型相关的酵母菌展示抗原来克服这些局限性，以在哺乳动物细胞系中进行数轮选择后选择噬菌体抗体输出。我们使用这种方法来生成针对酵母菌展示的EphA2和CD44的几种人噬菌体抗体。抗体结合酵母展示的和哺乳动物细胞的表面抗原，并在与哺乳动物细胞结合后被内吞。该方法可推广到许多哺乳动物细胞表面蛋白，导致功能性内在化抗体的产生，并且不需要抗原表达和纯化即可产生抗体。

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