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<p>T-cell acute lymphoblastic leukemia (T-ALL), with few targeted therapies in the clinic, is the most problematic blood cancer. Here, we report an immuno-nanoinhibitor (iNAHI) that selectively delivers volasertib, an inhibitor of polo-like kinase 1 (PLK1), to T-ALL cells for high-efficacy molecular targeted therapy. The iNAHI, with an average of 3.5 daratumumab antibodies per nanoparticle, possessed a high inhibitor-to-antibody ratio of ca. 600, enabling effective delivery of volasertib at a low antibody dosage. As a result, iNAHI significantly boosts PLK1 downregulation, cell cycle blockade and apoptosis in CD38-positive T-ALL cells compared with free volasertib and nontargeted nanoinhibitor. Therapeutic studies in mice with orthotopic CCRF-CEM T-ALL revealed potent suppression of leukemia burden and extramedullary invasion at a low iNAHI dose of 9 mg volasertib equiv./kg, leading to significant survival benefits with negligible adverse effects. This immuno-nanoinhibitor provides a promising targeted treatment strategy for T-ALL.</p>

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Immuno-nanoinhibitor potentiates molecular targeted therapy of T-cell acute lymphoblastic leukemia

  • 期刊论文

  • 发表日期：

    2026年6月17日

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  • Chenming Li,
  • Zhenzhen Zhai,
  • Lin Chen,
  • Li Cao,
  • Huanli Sun,
  • Zhiyuan Zhong

摘要

T-cell acute lymphoblastic leukemia (T-ALL), with few targeted therapies in the clinic, is the most problematic blood cancer. Here, we report an immuno-nanoinhibitor (iNAHI) that selectively delivers volasertib, an inhibitor of polo-like kinase 1 (PLK1), to T-ALL cells for high-efficacy molecular targeted therapy. The iNAHI, with an average of 3.5 daratumumab antibodies per nanoparticle, possessed a high inhibitor-to-antibody ratio of ca. 600, enabling effective delivery of volasertib at a low antibody dosage. As a result, iNAHI significantly boosts PLK1 downregulation, cell cycle blockade and apoptosis in CD38-positive T-ALL cells compared with free volasertib and nontargeted nanoinhibitor. Therapeutic studies in mice with orthotopic CCRF-CEM T-ALL revealed potent suppression of leukemia burden and extramedullary invasion at a low iNAHI dose of 9 mg volasertib equiv./kg, leading to significant survival benefits with negligible adverse effects. This immuno-nanoinhibitor provides a promising targeted treatment strategy for T-ALL.