Scholarlink

<p>Antigen-presenting cells phagocytose tumor cells and subsequently cross-present tumor-derived antigens. However, these processes are impeded by phagocytosis checkpoints and inefficient cytosolic transport of antigenic peptides from phagolysosomes. Here, using a microbial-inspired strategy, we engineered an antibody–toxin conjugate (ATC) that targets the ‘don’t eat me’ signal CD47 linked to the bacterial toxin listeriolysin O from the intracellular bacterium <i>Listeria monocytogenes</i> via a cleavable linker (CD47–LLO). CD47–LLO promotes cancer cell phagocytosis by macrophages followed by LLO release and activation to form pores on phagolysosomal membranes that enhance antigen cross-presentation of tumor-derived peptides and activate cytosolic immune sensors. CD47–LLO treatment in vivo significantly inhibited the growth of both localized and metastatic breast and melanoma tumors and improved animal survival as a monotherapy or in combination with checkpoint blockade. Together, these results demonstrate that designing ATCs to promote immune recognition of tumor cells represents a promising therapeutic strategy for treating multiple cancers.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

An antibody–toxin conjugate targeting CD47 linked to the bacterial toxin listeriolysin O for cancer immunotherapy

  • 期刊论文

  • 发表日期：

    2025年2月25日

查看全文
  • Benjamin R. Schrank,
  • Yifan Wang,
  • Annette Wu,
  • Nhat Tran,
  • DaeYong Lee,
  • Jared Edwards,
  • Kristin Huntoon,
  • Shiyan Dong,
  • JongHoon Ha,
  • Yifan Ma,
  • Adam J. Grippin,
  • Seong Dong Jeong,
  • Abin Antony,
  • Mengyu Chang,
  • Minjeong Kang,
  • Thomas D. Gallup,
  • Albert C. Koong,
  • Jing Li,
  • Kyuson Yun,
  • Betty Y. S. Kim,
  • Wen Jiang

摘要

Antigen-presenting cells phagocytose tumor cells and subsequently cross-present tumor-derived antigens. However, these processes are impeded by phagocytosis checkpoints and inefficient cytosolic transport of antigenic peptides from phagolysosomes. Here, using a microbial-inspired strategy, we engineered an antibody–toxin conjugate (ATC) that targets the ‘don’t eat me’ signal CD47 linked to the bacterial toxin listeriolysin O from the intracellular bacterium Listeria monocytogenes via a cleavable linker (CD47–LLO). CD47–LLO promotes cancer cell phagocytosis by macrophages followed by LLO release and activation to form pores on phagolysosomal membranes that enhance antigen cross-presentation of tumor-derived peptides and activate cytosolic immune sensors. CD47–LLO treatment in vivo significantly inhibited the growth of both localized and metastatic breast and melanoma tumors and improved animal survival as a monotherapy or in combination with checkpoint blockade. Together, these results demonstrate that designing ATCs to promote immune recognition of tumor cells represents a promising therapeutic strategy for treating multiple cancers.