次世代の抗体-薬物複合体（ADC）の創出に向けた新規リンカーの開発

DOI Web Site Web Site PubMed 参考文献39件
  • 土釜 恭直
    テキサスセラピューティクス研究所 ブラウン分子医学研究所 テキサス大学ヘルスサイエンスセンター ヒューストン

書誌事項

タイトル別名
  • Novel Chemical Linkers for Next-generation Antibody-drug Conjugates(ADCs)
  • Symposium Review 次世代の抗体-薬物複合体(ADC)の創出に向けた新規リンカーの開発
  • Symposium Review ジセダイ ノ コウタイ-ヤクブツ フクゴウタイ(ADC)ノ ソウシュツ ニ ムケタ シンキ リンカー ノ カイハツ

この論文をさがす

抄録

<p>Antibody-drug conjugates (ADCs), monoclonal antibodies conjugated with highly potent drugs (payloads) through chemical linkers, are an emerging class of therapeutic agents for cancer chemotherapy. Their clinical success has been demonstrated by the 4 ADCs already approved by the U.S. Food and Drug Administration (FDA), and more than 60 promising ADCs now in clinical trials. Further advancement of this novel molecular platform could potentially revolutionize current strategies and regimens for treating cancers. The linker structure and antibody-linker conjugation modality critically contribute to ADC homogeneity, circulation stability, pharmacokinetic profiles, tolerability, and overall treatment efficacy. Despite extensive efforts to improve these parameters, most ADC linkers used to date possess linear structures, and therefore accommodate only single payloads. The clinical potential of branched ADC linkers, enabling the installation of two payload molecules, remains unexplored because of the lack of efficient conjugation methods. In addition, according to a recent report, the stability of enzymatically cleavable linkers in mouse circulation is another crucial factor for the successful evaluation of ADCs in preclinical studies. In this review, I present my research group's effort to develop both branched linkers and efficient conjugation methods for constructing dual-loading ADCs with high homogeneity and enhanced potency. I also present a novel tripeptide ADC linker with enhanced stability in mouse circulation. Multidisciplinary experience, approaches, and collaboration are key to successfully advancing our ADC research programs. I herein describe how my experience in the U.S. has helped to develop and manage complex biomedical research projects in a small academic laboratory setting.</p>

収録刊行物

  • 薬学雑誌

    薬学雑誌 139 (2), 209-219, 2019-02-01

    公益社団法人 日本薬学会

参考文献 (39)*注記

もっと見る

キーワード

詳細情報 詳細情報について

問題の指摘

ページトップへ