A peptide inhibitor of antibody-dependent cell-mediated cytotoxicity against EGFR/folate receptor-α double positive cells

Koichi Sasaki, Yoshiki Miyashita, Daisuke Asai, Daiki Funamoto, Kazuki Sato, Yoko Yamaguchi, Yuji Mishima, Tadafumi Iino, Shigeo Takaishi, Jun Nagano, Akihiro Kishimura, Takeshi Mori, Yoshiki Katayama

研究成果: Contribution to journalArticle査読

4 被引用数 (Scopus)

抄録

Antibody-dependent cell-mediated cytotoxicity (ADCC) is caused by natural killer (NK) cells upon recognition of antigen-bound IgG via FcγRIIIa. This mechanism is crucial for cytolysis of pathogen-infected cells and monoclonal antibody (mAb)-mediated elimination of cancer cells. However, there is concern that mAb-based cancer therapy induces ADCC against non-target cells expressing antigens. To date, no strategy has been reported to enhance the selectivity of ADCC to protect non-target cells expressing antigens. Here, we introduce a model inhibitor which specifically blocks ADCC of anti-EGFR mAbs towards EGFR/folate receptor α (FRα) double positive cells. This inhibitor recruits mAbs on the FRα of the cell surface independent of Fab antigen recognition. The resulting ternary and/or quaternary complexes formed on the cell surface suppress signal transduction of FcγRIIIa in NK cells, consequently leading to more specific ADCC.

本文言語英語
ページ(範囲)783-788
ページ数6
ジャーナルMedChemComm
9
5
DOI
出版ステータス出版済み - 2018

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry

フィンガープリント 「A peptide inhibitor of antibody-dependent cell-mediated cytotoxicity against EGFR/folate receptor-α double positive cells」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル