World journal of urology · 2025
Bispecific antibodies in metastatic castration-resistant prostate cancer: therapeutic strategies and frontier advances.
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He Jia Wei, Li Pei Zhen, Huang Zi Xuan
Аннотация
PURPOSE: To summarize the therapeutic strategies, efficacy, safety, and advances of bispecific antibodies (BsAbs) in metastatic castration-resistant prostate cancer (mCRPC), and analyze their current challenges and future directions.
METHODS: A comprehensive review of latest BsAb research in mCRPC was conducted. Studies on BsAbs targeting key antigens (PSMA, STEAP1, PSCA) were collated, covering their design, mechanisms, preclinical/clinical data. Efficacy (PSA response, tumor regression), toxicity (cytokine release syndrome [CRS]), and limitations of BsAb constructs were analyzed.
RESULTS: BsAbs (especially bispecific T-cell engagers [BiTEs]) act by redirecting T cells to lyse tumor cells via dual targeting of tumor antigens and T-cell receptors. BsAbs like AMG 160, MOR209/ES414, and Acapatamab showed potent antitumor activity-30.4% of mCRPC patients had confirmed PSA responses in Acapatamab's phase I study. However, clinical use is limited by dose-limiting toxicities (CRS up to 98.2%), immunogenicity, and immunosuppressive tumor microenvironment. Strategies like optimizing BsAb structure, adding costimulatory signals, and combining with checkpoint inhibitors are explored to improve efficacy and reduce toxicity.
CONCLUSIONS: BsAbs are a promising therapeutic strategy for mCRPC, with potential to improve outcomes in this poorly treatable disease. Addressing challenges (toxicity, tumor microenvironment, response durability) via research and trials is key to unlocking their full potential. Future research should focus on optimizing constructs, exploring novel targets, and developing combination therapies to advance BsAbs in prostate cancer.
METHODS: A comprehensive review of latest BsAb research in mCRPC was conducted. Studies on BsAbs targeting key antigens (PSMA, STEAP1, PSCA) were collated, covering their design, mechanisms, preclinical/clinical data. Efficacy (PSA response, tumor regression), toxicity (cytokine release syndrome [CRS]), and limitations of BsAb constructs were analyzed.
RESULTS: BsAbs (especially bispecific T-cell engagers [BiTEs]) act by redirecting T cells to lyse tumor cells via dual targeting of tumor antigens and T-cell receptors. BsAbs like AMG 160, MOR209/ES414, and Acapatamab showed potent antitumor activity-30.4% of mCRPC patients had confirmed PSA responses in Acapatamab's phase I study. However, clinical use is limited by dose-limiting toxicities (CRS up to 98.2%), immunogenicity, and immunosuppressive tumor microenvironment. Strategies like optimizing BsAb structure, adding costimulatory signals, and combining with checkpoint inhibitors are explored to improve efficacy and reduce toxicity.
CONCLUSIONS: BsAbs are a promising therapeutic strategy for mCRPC, with potential to improve outcomes in this poorly treatable disease. Addressing challenges (toxicity, tumor microenvironment, response durability) via research and trials is key to unlocking their full potential. Future research should focus on optimizing constructs, exploring novel targets, and developing combination therapies to advance BsAbs in prostate cancer.