Tumor-Targeted Nonablative Radiation Promotes Solid Tumor CAR T-cell Therapy Efficacy.

Autor:	Quach HT; Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York., Skovgard MS; Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York., Villena-Vargas J; Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York., Bellis RY; Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York., Chintala NK; Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York., Amador-Molina A; Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York., Bai Y; Department of Cardiothoracic Surgery, Weill Cornell Medicine, New York, New York.; Meyer Cancer Center, Weill Cornell Medicine, New York, New York., Banerjee S; Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York., Saini J; Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York., Xiong Y; Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York., Vista WR; Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York., Byun AJ; Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York., De Biasi A; Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York., Zeltsman M; Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York., Mayor M; Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York., Morello A; Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York., Mittal V; Department of Cardiothoracic Surgery, Weill Cornell Medicine, New York, New York.; Meyer Cancer Center, Weill Cornell Medicine, New York, New York., Gomez DR; Thoracic Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York., Rimner A; Thoracic Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York., Jones DR; Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York., Adusumilli PS; Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.; Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, New York.
Jazyk:	angličtina
Zdroj:	Cancer immunology research [Cancer Immunol Res] 2023 Oct 04; Vol. 11 (10), pp. 1314-1331.
DOI:	10.1158/2326-6066.CIR-22-0840
Abstrakt:	Infiltration of tumor by T cells is a prerequisite for successful immunotherapy of solid tumors. In this study, we investigate the influence of tumor-targeted radiation on chimeric antigen receptor (CAR) T-cell therapy tumor infiltration, accumulation, and efficacy in clinically relevant models of pleural mesothelioma and non-small cell lung cancers. We use a nonablative dose of tumor-targeted radiation prior to systemic administration of mesothelin-targeted CAR T cells to assess infiltration, proliferation, antitumor efficacy, and functional persistence of CAR T cells at primary and distant sites of tumor. A tumor-targeted, nonablative dose of radiation promotes early and high infiltration, proliferation, and functional persistence of CAR T cells. Tumor-targeted radiation promotes tumor-chemokine expression and chemokine-receptor expression in infiltrating T cells and results in a subpopulation of higher-intensity CAR-expressing T cells with high coexpression of chemokine receptors that further infiltrate distant sites of disease, enhancing CAR T-cell antitumor efficacy. Enhanced CAR T-cell efficacy is evident in models of both high-mesothelin-expressing mesothelioma and mixed-mesothelin-expressing lung cancer-two thoracic cancers for which radiotherapy is part of the standard of care. Our results strongly suggest that the use of tumor-targeted radiation prior to systemic administration of CAR T cells may substantially improve CAR T-cell therapy efficacy for solid tumors. Building on our observations, we describe a translational strategy of "sandwich" cell therapy for solid tumors that combines sequential metastatic site-targeted radiation and CAR T cells-a regional solution to overcome barriers to systemic delivery of CAR T cells. (©2023 American Association for Cancer Research.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu