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Background <p>Relapsed/refractory acute myeloid leukemia (AML) in children remains challenging due to leukemia stem cells (LSCs) and poor immunogenicity. This study aimed to construct a novel immunoconjugate combining BCG heat shock protein 70 (HSP70) with an anti-CD123 monoclonal antibody (MAb) and evaluate its targeted anti-leukemic efficacy and mechanisms.</p> Methods <p>The conjugate (HSP70-MAb) was synthesized via SPDP crosslinker and characterized by ESI-MS and UV spectrophotometry. Antigen-binding activity was assessed by flow cytometry. In vitro, autologous T-cell proliferation (CFSE staining), IFN-γ secretion (ELISA), and cytotoxic activity (LDH release) were assessed. In vivo, the anti-leukemic effect was evaluated in a MOLM13 xenograft nude mouse model.</p> Results <p>The HSP70-MAb conjugate showed high purity (96.2 ± 1.5)% and near 1:1 molar conjugation efficiency, retaining antigen-binding activity. In vitro, HSP70-MAb significantly enhanced autologous T-lymphocyte proliferation and IFN-γ secretion, and markedly increased CTL-mediated cytotoxicity against CD123⁺ AML cells in an E:T ratio-dependent manner. In vivo, HSP70-MAb significantly reduced tumor volume, strongly stimulated MOLM13-specific Th1 cell generation, and induced coagulative necrosis with abundant CD8⁺ T lymphocyte infiltration in tumor tissues.</p> Conclusion <p>The BCG HSP70/anti-CD123 immunoconjugate exerts potent targeted anti-leukemic effects by enhancing immunogenicity and T-cell immunity, representing a promising therapeutic candidate for childhood AML, especially relapsed/refractory cases.</p> Impact <p><UnorderedList Mark="Bullet"> <ItemContent> <p>We constructed an HSP70/anti-CD123 MAb conjugate retaining binding/immune activity, exerting potent targeted anti-leukemic effects via enhanced immunogenicity and T-cell immunity in vitro/in vivo.</p> </ItemContent> <ItemContent> <p>Targeting LSCs/MRD, it outperforms single agents, filling gaps in pediatric AML CD123 + LSC targeted immune enhancement.</p> </ItemContent> <ItemContent> <p>This conjugate offers a new immunotherapy, laying preclinical foundations for LSC/MRD-clearing anti-AML drugs.</p> </ItemContent> <ItemContent> <p>It establishes an HSP70-mAb coupling method, providing new ideas for other hematologic/solid tumors.</p> </ItemContent> <ItemContent> <p>The high-quality conjugate shows strong anti-tumor effects with no noted toxicity, accelerating its pediatric oncology translational application.</p> </ItemContent> </UnorderedList></p>

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Targeted efficacy of BCG Hsp70–anti-CD123 immunoconjugate in childhood acute myeloid leukemia

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月15日

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  • Xiao-Ling Li,
  • Wenting Pei,
  • Chun-lei Liu

摘要

Background

Relapsed/refractory acute myeloid leukemia (AML) in children remains challenging due to leukemia stem cells (LSCs) and poor immunogenicity. This study aimed to construct a novel immunoconjugate combining BCG heat shock protein 70 (HSP70) with an anti-CD123 monoclonal antibody (MAb) and evaluate its targeted anti-leukemic efficacy and mechanisms.

Methods

The conjugate (HSP70-MAb) was synthesized via SPDP crosslinker and characterized by ESI-MS and UV spectrophotometry. Antigen-binding activity was assessed by flow cytometry. In vitro, autologous T-cell proliferation (CFSE staining), IFN-γ secretion (ELISA), and cytotoxic activity (LDH release) were assessed. In vivo, the anti-leukemic effect was evaluated in a MOLM13 xenograft nude mouse model.

Results

The HSP70-MAb conjugate showed high purity (96.2 ± 1.5)% and near 1:1 molar conjugation efficiency, retaining antigen-binding activity. In vitro, HSP70-MAb significantly enhanced autologous T-lymphocyte proliferation and IFN-γ secretion, and markedly increased CTL-mediated cytotoxicity against CD123⁺ AML cells in an E:T ratio-dependent manner. In vivo, HSP70-MAb significantly reduced tumor volume, strongly stimulated MOLM13-specific Th1 cell generation, and induced coagulative necrosis with abundant CD8⁺ T lymphocyte infiltration in tumor tissues.

Conclusion

The BCG HSP70/anti-CD123 immunoconjugate exerts potent targeted anti-leukemic effects by enhancing immunogenicity and T-cell immunity, representing a promising therapeutic candidate for childhood AML, especially relapsed/refractory cases.

Impact

We constructed an HSP70/anti-CD123 MAb conjugate retaining binding/immune activity, exerting potent targeted anti-leukemic effects via enhanced immunogenicity and T-cell immunity in vitro/in vivo.

Targeting LSCs/MRD, it outperforms single agents, filling gaps in pediatric AML CD123 + LSC targeted immune enhancement.

This conjugate offers a new immunotherapy, laying preclinical foundations for LSC/MRD-clearing anti-AML drugs.

It establishes an HSP70-mAb coupling method, providing new ideas for other hematologic/solid tumors.

The high-quality conjugate shows strong anti-tumor effects with no noted toxicity, accelerating its pediatric oncology translational application.