title: A variety of human monoclonal antibodies against epidermal growth factor receptor isolated from a phage antibody library.
abstract: When the technology for constructing human antibody (Ab) libraries using a phage-display system was developed, many researchers in Ab-related fields anticipated that it would be widely applied to the development of pharmaceutical drugs against various diseases, including cancers. However, successful examples of such applications are very limited. Moreover, researchers who utilize phage-display technology now show divergent ways of thinking about phage Ab libraries. For example, there is debate about what should be the source of VHand VLgenes for the construction of libraries to cover the whole repertoire of Abs present in the human body. In the immune system, the introduction of mutations into V genes followed by selection based on binding activity, termed Ab maturation, is required for the production of Abs exhibiting high affinity to the antigen (Ag). Therefore, introduction of mutations and selection are required for isolation of Abs with high affinity after isolation of clones from phage Ab libraries. We constructed a large human Ab library termed AIMS, developed a screening method termed ICOS, and succeeded in isolating many human monoclonal Abs (mAbs) that specifically and strongly bind to various tumor-associated Ags. Eight anti-EGFR mAbs were included, which we characterized. These mAbs showed various different activities against EGFR-expressing cancer cells. In this paper, we describe these data and discuss the possibility and necessity that the mAbs isolated from the AIMS library might be developed as therapeutic drugs against cancers without introduction of mutations.
authors.affiliation: Division of Antibody Project, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi, Japan.
authors.forename: Gene
authors.initials: G
authors.lastname: Kurosawa
authors.affiliation: Perseus Proteomics Inc., Tokyo, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Kondo
authors.affiliation: Division of Antibody Project, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi, Japan. Electronic address: kurosawa@fujita-hu.ac.jp.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Kurosawa
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D066246:ErbB Receptors / Q000276:immunology*; D006801:Humans; D008807:Mice, Inbred BALB C; D019151:Peptide Library; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D019151:Peptide Library; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: Ab repertoire; Anti-EGFR Ab; Mutation; Phage-display Ab library; Therapeutic Ab