Probiotic-derived glucose oxidase exerts therapeutic efficacy against pediatric B-cell acute lymphoblastic leukemia

Recent advances in therapy have significantly improved long-term survival in pediatric B-cell acute lymphoblastic leukemia (B-ALL). However, relapse still occurs in 15-20 % of cases, and post-relapse survival rates remain suboptimal at 30-60 %. Therefore, novel therapeutic strategies effective against both primary and relapsed B-ALL are needed. In this study, we treated B-ALL cells with the cell-free culture supernatants (CFCS) of various probiotic strains and found that Aspergillus niger exerted the most potent inhibitory effect on B-ALL cell viability. Liquid chromatography-mass spectrometry analysis following fractionation of the CFCS identified glucose oxidase (GOx) as a key component enriched in the active antitumor fraction. GOx significantly reduced the viability of Reh cells and patient-derived B-ALL cells while exhibiting minimal cytotoxicity against peripheral blood mononuclear cells. Mechanistically, GOx reduced glucose levels and increased hydrogen peroxide levels in the culture medium. Encapsulation of GOx in calcium nanoparticles significantly prolonged survival in a patient-derived xenograft mouse model established from relapsed B-ALL. GOx induced both apoptotic and necrotic cell death in B-ALL cells and exhibited additive antitumor activity when combined with vincristine or doxorubicin. These findings suggest that GOx selectively induces cell death in B-ALL cells and may enhance therapeutic efficacy when used in combination with standard chemotherapeutics.