γδ-Enriched CAR-T cell therapy for bone metastatic castrate-resistant prostate cancer.

Autor: Frieling JS; Department of Tumor Biology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA., Tordesillas L; Department of Immunology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA., Bustos XE; Department of Immunology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA., Ramello MC; Department of Immunology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA., Bishop RT; Department of Tumor Biology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA., Cianne JE; Department of Immunology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA., Snedal SA; Department of Immunology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA., Li T; Department of Tumor Biology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA., Lo CH; Department of Tumor Biology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA., de la Iglesia J; Department of Pathology Research, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA., Roselli E; Department of Immunology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA., Benzaïd I; Department of Immunology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA., Wang X; Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA., Kim Y; Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA., Lynch CC; Department of Tumor Biology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA., Abate-Daga D; Department of Immunology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, USA.
Jazyk: angličtina
Zdroj: Science advances [Sci Adv] 2023 May 03; Vol. 9 (18), pp. eadf0108. Date of Electronic Publication: 2023 May 03.
DOI: 10.1126/sciadv.adf0108
Abstrakt: Immune checkpoint blockade has been largely unsuccessful for the treatment of bone metastatic castrate-resistant prostate cancer (mCRPC). Here, we report a combinatorial strategy to treat mCRPC using γδ-enriched chimeric antigen receptor (CAR) T cells and zoledronate (ZOL). In a preclinical murine model of bone mCRPC, γδ 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-approved bisphosphonate prescribed to mitigate pathological fracture in mCRPC patients, resulted in CAR-independent activation of γδ CAR-T cells, increased cytokine secretion, and enhanced antitumor efficacy. These data show that the activity of the endogenous Vγ9Vδ2 T cell receptor is preserved in CAR-T cells, allowing for dual-receptor recognition of tumor cells. Collectively, our findings support the use of γδ CAR-T cell therapy for mCRPC treatment.
Databáze: MEDLINE
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