Antibody-drug conjugate halts aggressive prostate cancer in mouse models

An antibody-drug conjugate targeting the surface protein STEAP1 eliminated metastatic prostate tumors in multiple mouse models, according to a study published in Science Translational Medicine. The conjugate, called STEAP1-ADC, links an anti-STEAP1 monoclonal antibody to a topoisomerase I inhibitor payload. In mice bearing human prostate cancer xenografts with high STEAP1 expression, a single dose eradicated established tumors and prevented recurrence for at least 90 days. The treatment also cleared metastases in the liver, lungs, and lymph nodes. STEAP1 is overexpressed in the majority of castration-resistant prostate cancers but largely absent from healthy adult tissues, giving the conjugate a wide therapeutic window. In toxicology studies, non-human primates tolerated doses well above the therapeutic range with no dose-limiting toxicities. The research team, led by investigators at the University of California, San Francisco, and the Parker Institute for Cancer Immunotherapy, says the data support advancing STEAP1-ADC toward first-in-human trials for metastatic castration-resistant prostate cancer, a disease with few effective options once standard hormonal therapies fail.