XOMA Corp., 2910 Seventh St., Berkeley, CA 94710, United States.
J Immunol Methods. 2013 May 31;391(1-2):60-71. doi: 10.1016/j.jim.2013.02.010. Epub 2013 Feb 27.
Phage display antibody libraries have a proven track record for the discovery of therapeutic human antibodies, increasing the demand for large and diverse phage antibody libraries for the discovery of new therapeutics. We have constructed naïve antibody phage display libraries in both Fab and scFv formats, with each library having more than 250 billion clones that encompass the human antibody repertoire. These libraries show high fidelity in open reading frame and expression percentages, and their V-gene family distribution, VH-CDR3 length and amino acid usage mirror the natural diversity of human antibodies. Both the Fab and scFv libraries show robust sequence diversity in target-specific binders and differential V-gene usage for each target tested, supporting the use of libraries that utilize multiple display formats and V-gene utilization to maximize antibody-binding diversity. For each of the targets, clones with picomolar affinities were identified from at least one of the libraries and for the two targets assessed for activity, functional antibodies were identified from both libraries.
噬菌体展示抗体文库在发现治疗性人源抗体方面有着良好的记录，这增加了对用于发现新疗法的大型多样化噬菌体抗体文库的需求。我们构建了 Fab 和 scFv 两种形式的天然抗体噬菌体展示文库，每个文库包含超过 2500 亿个克隆，涵盖了人类抗体库。这些文库在开放阅读框和表达百分比方面具有很高的保真度，其 V 基因家族分布、VH-CDR3 长度和氨基酸使用情况反映了人类抗体的自然多样性。Fab 和 scFv 文库在针对特定靶点的结合物中均显示出强大的序列多样性，并且针对每个测试靶点的 V 基因使用情况也存在差异，这支持使用利用多种展示形式和 V 基因利用来最大限度提高抗体结合多样性的文库。对于每个靶点，至少从一个文库中鉴定出具有皮摩尔亲和力的克隆，并且对于评估活性的两个靶点，从两个文库中都鉴定出了功能性抗体。
