ArticlePediatric research2026
Targeted efficacy of BCG Hsp70-anti-CD123 immunoconjugate in childhood acute myeloid leukemia.
Article in Pediatric research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundRelapsed/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.
methodsThe 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.
resultsThe 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.
conclusionThe 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.
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Registered trials
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