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

Authors

Xiao-Ling Li, Wenting Pei, Chun-Lei Liu

Published in

Pediatric research. Jun 15, 2026. Epub Jun 15, 2026.

Abstract

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.
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.
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.
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.
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.

PMID:
42298015
Bibliographic data and abstract were imported from PubMed on 16 Jun 2026.

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