二重特異性抗体のタンパク質工学を駆使した高機能化

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タイトル別名
  • Functionalization of Bispecific Therapeutic Antibodies Based on Protein Engineering
  • Symposium Review 二重特異性抗体のタンパク質工学を駆使した高機能化
  • Symposium Review ニジュウ トクイセイ コウタイ ノ タンパクシツ コウガク オ クシ シタ コウキノウカ

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抄録

  Although antibodies have been used as molecularly targeted agents for difficult-to-treat diseases such as cancers, the high production costs associated with mammalian expression systems continue to be a drawback. In addition, the clinical efficacy of conventional IgG antibodies is limited. Several types of recombinant antibody (e.g. fused with anticancer drugs, multivalent, or multispecific) have been designed in efforts to develop next-generation antibodies with higher functionality. We used protein engineering to construct several anticancer recombinant antibodies by developing bispecific antibodies that induced specific antitumor effects against cancer cells through the recruitment of lymphocytes. We found that a humanized small bispecific antibody (Ex3) that targets epidermal growth factor receptor on tumor cells and CD3 on T lymphocytes had marked anticancer activity. Furthermore, the function of Ex3 was enhanced by fusion with the human Fc region, domain rearrangement, multimerization, and affinity maturation; a combination of these modifications showed at least additive cytotoxic effects. Interestingly, merely rearranging the domain order of Ex3 induced substantial cytotoxic enhancements, even though the structural format remained the same. Here, we describe our efforts to develop highly functional bispecific antibodies as next-generation therapeutic antibodies using protein engineering.<br>

収録刊行物

  • 薬学雑誌

    薬学雑誌 135 (7), 851-856, 2015-07-01

    公益社団法人 日本薬学会

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