Scholarlink

<p>Macrophages play a key role in immunity against solid tumors. However, their development and clinical applications are limited by their difficult-to-transfect nature, low proliferative capacity, and easily changing polarization states. The combination of chimeric antigen receptor (CAR) technology with macrophages to form chimeric antigen receptor macrophages (CAR-Ms) is an emerging strategy for adoptive cell therapy. In our previous study, we confirmed that anti-CD47 CAR-Ms have potential for ovarian cancer treatment. Here, we demonstrated that the introduction of IL-21 significantly increases the tumor-suppressive effect of anti-CD47 CAR-Ms against ovarian cancer. Specifically, IL-21-modified CAR-Ms with second-generation CARs targeting CD47 showed potent tumor cell-killing activity, both <i>in</i> vitro and in vivo, through direct and indirect pathways (direct phagocytosis and activation of cytotoxic T lymphocytes). In addition, an IL-21 modification significantly enhanced the tumor microenvironmental regulation of immunosuppression mediated by anti-CD47 CAR-Ms in vivo, thereby improving their therapeutic efficacy in a mouse model of ovarian cancer, without any obvious adverse effects. Taken together, these results suggest that anti-CD47 CAR-Ms combined with IL-21 is a promising treatment strategy for ovarian cancer.</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

IL-21 promotes the anti-tumor effect of anti-CD47 chimeric antigen receptor macrophages in ovarian cancer

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年12月23日

查看全文
  • Yizhao Chen,
  • Xiangling Zhu,
  • Yu Chen,
  • Zhaoyi Yang,
  • Zhaolei Shen,
  • Mengchen Chen,
  • Chong Liu,
  • Yuanyuan Zhou,
  • Huihui Wang,
  • Mengjuan Zhu,
  • Jiaqi Qiu,
  • Jinhua Huang,
  • Xintong Han,
  • Wei Wei,
  • Li Ruilin,
  • Wenming Hong,
  • Jiajie Tu

摘要

Macrophages play a key role in immunity against solid tumors. However, their development and clinical applications are limited by their difficult-to-transfect nature, low proliferative capacity, and easily changing polarization states. The combination of chimeric antigen receptor (CAR) technology with macrophages to form chimeric antigen receptor macrophages (CAR-Ms) is an emerging strategy for adoptive cell therapy. In our previous study, we confirmed that anti-CD47 CAR-Ms have potential for ovarian cancer treatment. Here, we demonstrated that the introduction of IL-21 significantly increases the tumor-suppressive effect of anti-CD47 CAR-Ms against ovarian cancer. Specifically, IL-21-modified CAR-Ms with second-generation CARs targeting CD47 showed potent tumor cell-killing activity, both in vitro and in vivo, through direct and indirect pathways (direct phagocytosis and activation of cytotoxic T lymphocytes). In addition, an IL-21 modification significantly enhanced the tumor microenvironmental regulation of immunosuppression mediated by anti-CD47 CAR-Ms in vivo, thereby improving their therapeutic efficacy in a mouse model of ovarian cancer, without any obvious adverse effects. Taken together, these results suggest that anti-CD47 CAR-Ms combined with IL-21 is a promising treatment strategy for ovarian cancer.