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In a preclinical murine model of bone mCRPC, \u03b3\u03b4 CAR-T cells targeting prostate stem cell antigen (PSCA) induced a rapid and significant regression of established tumors, combined with increased survival and reduced cancer-associated bone disease. Pretreatment with ZOL, a U.S. Food and Drug Administration\u2013approved bisphosphonate prescribed to mitigate pathological fracture in mCRPC patients, resulted in CAR-independent activation of \u03b3\u03b4 CAR-T cells, increased cytokine secretion, and enhanced antitumor efficacy. These data show that the activity of the endogenous V\u03b39V\u03b42 T cell receptor is preserved in CAR-T cells, allowing for dual-receptor recognition of tumor cells. Collectively, our findings support the use of \u03b3\u03b4 CAR-T cell therapy for mCRPC treatment.<\/jats:p>","DOI":"10.1126\/sciadv.adf0108","type":"journal-article","created":{"date-parts":[[2023,5,3]],"date-time":"2023-05-03T13:58:40Z","timestamp":1683122320000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":76,"title":["\u03b3\u03b4-Enriched CAR-T cell therapy for bone metastatic castrate-resistant prostate cancer"],"prefix":"10.1126","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2181-1836","authenticated-orcid":true,"given":"Jeremy S.","family":"Frieling","sequence":"first","affiliation":[{"name":"Department of Tumor Biology, H. 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