Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2025
B7-H3-liquid biopsy for the characterization and monitoring of the dynamic biology of prostate cancer.
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Ju Yong, Watson Joshua, Wang Jasmine J, Yen Ying-Tzu, Gevorkian Lilit, Chen Zijing, Tu Kai Han, Salumbides Brenda, Phung Aaron, Zhao Chen, Kim Hyoyong, Ji You-Ren, Zhang Ryan Y, Lee Junseok, Gong Jun, Scher Kevin, You Sungyong, Chen Jie-Fu, Tseng Hsian-Rong, Zhu Yazhen, Posadas Edwin M
Аннотация
BACKGROUND: B7-H3 is a promising target for cancer therapy, notably in prostate cancer (PCa), particularly in metastatic, castration-resistant PCa (mCRPC). With the development of B7-H3-targeted therapies, there is a need for a rapid, reliable, and cost-effective method to detect and monitor B7-H3 expression. Leveraging their abundance and stability, we developed a liquid biopsy assay using extracellular vesicles (EVs) for this purpose.
METHODS: B7-H3+ EVs were isolated using a B7-H3 antibody-mediated, click chemistry-based enrichment method. Antibodies were conjugated to methyltetrazine-grafted microbeads. EVs were isolated from 100 µL of plasma from metastatic, castration-sensitive PCa (mCSPC) (n = 43) and mCRPC (n = 103) patients and quantified using RT-qPCR of ACTB. Measurements were compared with the patient's disease status over time.
RESULTS: The assay detected higher B7-H3+ EVs in mCRPC than mCSPC and increased when mCSPC transitioned to mCRPC. Elevated B7-H3+ EVs were associated with lower overall survival (Hazard ratio (HR) 2.19, p = 0.01). In patients with serial plasma samples, B7-H3+ EV levels reflected treatment response and disease progression.
CONCLUSIONS: This B7-H3+ EV assay represents a significant advancement in utilizing tumor-derived EVs for a non-invasive, quantitative, and consistent real-time measurement of B7-H3. This assay warrants further development as a companion diagnostic for B7-H3 targeted therapies in PCa and other conditions.
METHODS: B7-H3+ EVs were isolated using a B7-H3 antibody-mediated, click chemistry-based enrichment method. Antibodies were conjugated to methyltetrazine-grafted microbeads. EVs were isolated from 100 µL of plasma from metastatic, castration-sensitive PCa (mCSPC) (n = 43) and mCRPC (n = 103) patients and quantified using RT-qPCR of ACTB. Measurements were compared with the patient's disease status over time.
RESULTS: The assay detected higher B7-H3+ EVs in mCRPC than mCSPC and increased when mCSPC transitioned to mCRPC. Elevated B7-H3+ EVs were associated with lower overall survival (Hazard ratio (HR) 2.19, p = 0.01). In patients with serial plasma samples, B7-H3+ EV levels reflected treatment response and disease progression.
CONCLUSIONS: This B7-H3+ EV assay represents a significant advancement in utilizing tumor-derived EVs for a non-invasive, quantitative, and consistent real-time measurement of B7-H3. This assay warrants further development as a companion diagnostic for B7-H3 targeted therapies in PCa and other conditions.