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<p>Natural killer (NK) cells are key components of innate immunity, playing a pivotal role in tumor recognition and eradication, and numerous NK cell-based immunotherapeutic approaches have been extensively investigated for cancer treatment. Here, we develop leukemia-targeting NK cell nanoengagers, termed AaLS/aCD16Nb/aCD13Nb, by simultaneously displaying NK cell-engaging nanobodies (aCD16Nb) and acute myeloid leukemia (AML)-targeting nanobodies (aCD13Nb) on lumazine synthase (AaLS) protein nanoparticles. The AaLS/aCD16Nb/aCD13Nb nanoengagers effectively bind to both NK cells and AML cells, thereby facilitating selective engagement of NK cells with leukemic targets. Through this targeted engagement, the AaLS/aCD16Nb/aCD13Nb nanoengagers promote NK cell activation, leading to enhanced interferon gamma (IFN-γ) production and robust AML cell killing in vitro. Furthermore, in AML-engraft mouse models, administration of the AaLS/aCD16Nb/aCD13Nb nanoengagers significantly reduce leukemic burden across multiple tissues, with pronounced effects in the bone marrow niche, and extend overall survival in two independent AML (U937 and THP-1) engrafted models. Collectively, our study demonstrates that this dual-ligand-displaying nanoengager platform represents a promising and potent anti-leukemic strategy, offering a multifunctional protein nanoparticles-based approach for AML immunotherapy that may be broadly adaptable to other malignancies.</p> Graphical abstract <p></p>

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Leukemia-targeting NK cell nanoengagers effectively promote robust NK activation and potent anti-acute myeloid leukemia response

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月6日

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  • Hyo Jeong Kim,
  • Heejin Jun,
  • Hyun Bin Lee,
  • Soomin Eom,
  • Junsu Kim,
  • Jun Pyo Jeon,
  • Sung Ho Park,
  • Sebyung Kang

摘要

Natural killer (NK) cells are key components of innate immunity, playing a pivotal role in tumor recognition and eradication, and numerous NK cell-based immunotherapeutic approaches have been extensively investigated for cancer treatment. Here, we develop leukemia-targeting NK cell nanoengagers, termed AaLS/aCD16Nb/aCD13Nb, by simultaneously displaying NK cell-engaging nanobodies (aCD16Nb) and acute myeloid leukemia (AML)-targeting nanobodies (aCD13Nb) on lumazine synthase (AaLS) protein nanoparticles. The AaLS/aCD16Nb/aCD13Nb nanoengagers effectively bind to both NK cells and AML cells, thereby facilitating selective engagement of NK cells with leukemic targets. Through this targeted engagement, the AaLS/aCD16Nb/aCD13Nb nanoengagers promote NK cell activation, leading to enhanced interferon gamma (IFN-γ) production and robust AML cell killing in vitro. Furthermore, in AML-engraft mouse models, administration of the AaLS/aCD16Nb/aCD13Nb nanoengagers significantly reduce leukemic burden across multiple tissues, with pronounced effects in the bone marrow niche, and extend overall survival in two independent AML (U937 and THP-1) engrafted models. Collectively, our study demonstrates that this dual-ligand-displaying nanoengager platform represents a promising and potent anti-leukemic strategy, offering a multifunctional protein nanoparticles-based approach for AML immunotherapy that may be broadly adaptable to other malignancies.

Graphical abstract