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<p>Chimeric antigen receptor macrophages (CAR-M) therapy holds significant clinical potential, while its application is severely compromised by poor in vivo colonization and limited persistence. Here, we report a 3D-printed implantable CAR-M (iCAR-M) system, composed of a gelatin methacrylate (GelMA) scaffold loaded with IL13Rα2-targeting CAR-M, and signal regulatory protein-α-overexpressing extracellular vesicles (SIRPα-EVs). Functioning as a bioactive reservoir, the porous hydrogel mitigates anoikis and promotes nutrient transport, markedly elevating CAR-M viability and increasing the frequency of activated macrophages in mice from ~ 5% to ~ 30% after 7 days. Mechanistically, the co-released SIRPα-EVs mask CD47 on tumor cells to abrogate the “don’t eat me” signal, synergizing with CAR-mediated phagocytosis. In a 4T1 post-surgery model, this locoregional delivery system significantly inhibited tumor recurrence and remodeled the immunosuppressive microenvironment, boosting CD80⁺ macrophage polarization ~ 24% and CD8<sup>+</sup> T-cell activation ~ 26%. Collectively, the iCAR-M functions as an engineered immune niche, integrating biomaterial-assisted persistence with checkpoint blockade to overcome solid tumor resistance.</p> Graphical abstract <p></p>

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3D-printed implantable CAR-macrophages for post-surgery cancer immunotherapy

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月9日

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  • Dingmeng Nie,
  • Yang Shen,
  • Yangtao Xu,
  • Xiao Hu,
  • Jiayang Qiu,
  • Xinyao Hu,
  • Qian-Fang Meng,
  • Peng She,
  • Lang Rao,
  • Qinqin Huang

摘要

Chimeric antigen receptor macrophages (CAR-M) therapy holds significant clinical potential, while its application is severely compromised by poor in vivo colonization and limited persistence. Here, we report a 3D-printed implantable CAR-M (iCAR-M) system, composed of a gelatin methacrylate (GelMA) scaffold loaded with IL13Rα2-targeting CAR-M, and signal regulatory protein-α-overexpressing extracellular vesicles (SIRPα-EVs). Functioning as a bioactive reservoir, the porous hydrogel mitigates anoikis and promotes nutrient transport, markedly elevating CAR-M viability and increasing the frequency of activated macrophages in mice from ~ 5% to ~ 30% after 7 days. Mechanistically, the co-released SIRPα-EVs mask CD47 on tumor cells to abrogate the “don’t eat me” signal, synergizing with CAR-mediated phagocytosis. In a 4T1 post-surgery model, this locoregional delivery system significantly inhibited tumor recurrence and remodeled the immunosuppressive microenvironment, boosting CD80⁺ macrophage polarization ~ 24% and CD8+ T-cell activation ~ 26%. Collectively, the iCAR-M functions as an engineered immune niche, integrating biomaterial-assisted persistence with checkpoint blockade to overcome solid tumor resistance.

Graphical abstract