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<p>Natural killer (NK)/T-cell lymphomas are a highly aggressive lymphoma subtype common in East Asia and Latin America. To develop a therapeutic monoclonal antibody (mAb) against it, BALB/c mice were alternately immunized with two vigorous NK lymphoma cell lines. After hybridization, culture supernatants of the hybridoma clones were added to a third NK lymphoma cell line not used for immunization, and the antibodies were screened for direct cytolytic activity. Results showed that the newly established mAb, named mAb ANAP, induced immediate cell death against NK lymphoma cells in a cytoskeleton-dependent manner, which was also complement-, antibody-dependent cell-mediated cytotoxicity-, and caspase-independent, forming large pores on target cell surface within 20&#xa0;min; mAb ANAP did not injure normal cells and could bind to the ITGA4 (CD49d). Contrary to existing anti-ITGA4 antibodies, which did not exhibit any destructive activity against NK lymphoma, ANAP antibody has promising potential as a therapeutic agent for NK lymphoma.</p>

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Novel anti-ITGA4 monoclonal antibody induces cell death via large pore formation in NK/T-cell lymphoma cells

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月30日

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  • Shiori Takeuchi,
  • Yasuhiko Ito,
  • Shuji Matsuoka,
  • Masaaki Abe,
  • Hiromichi Tsurui,
  • Yoshiya Horimoto,
  • Takeshi Fukuhara,
  • Takeshi Hirano,
  • Natsuko Mizutani,
  • Takumi Ito,
  • Ryo Hatano,
  • Atsuhito Nakao,
  • Yasuhisa Terao,
  • Mari Kitade,
  • Yoshitomo Hamano,
  • Hiroyuki Takamatsu,
  • Hiroshi Matsuoka,
  • Tetsuya Nakatsura,
  • Hideo Yagita,
  • Ko Okumura,
  • Atsuo Itakura

摘要

Natural killer (NK)/T-cell lymphomas are a highly aggressive lymphoma subtype common in East Asia and Latin America. To develop a therapeutic monoclonal antibody (mAb) against it, BALB/c mice were alternately immunized with two vigorous NK lymphoma cell lines. After hybridization, culture supernatants of the hybridoma clones were added to a third NK lymphoma cell line not used for immunization, and the antibodies were screened for direct cytolytic activity. Results showed that the newly established mAb, named mAb ANAP, induced immediate cell death against NK lymphoma cells in a cytoskeleton-dependent manner, which was also complement-, antibody-dependent cell-mediated cytotoxicity-, and caspase-independent, forming large pores on target cell surface within 20 min; mAb ANAP did not injure normal cells and could bind to the ITGA4 (CD49d). Contrary to existing anti-ITGA4 antibodies, which did not exhibit any destructive activity against NK lymphoma, ANAP antibody has promising potential as a therapeutic agent for NK lymphoma.