ArticleProceedings of the National Academy of Sciences of the United States of America2024
Proton radiation boosts the efficacy of mesothelin-targeting chimeric antigen receptor T cell therapy in pancreatic cancer.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed.
- Barriers and Blueprints: Next-Generation Engineering Strategies for CAR-T Cell Therapy in Gastrointestinal Tumors.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Challenges and opportunities in combining radiotherapy and immunotherapy for localized pancreatic cancer.Nature reviews. Gastroenterology & hepatology · 2026Review
- Advances, challenges, and innovative strategies of CAR-T cell therapy in pancreatic cancer.Biomarker research · 2026Review
- Harnessing the sparing effect of FLASH-RT: From phenomenon observation, radiophysical determinants to molecular mechanisms and synergistic strategies.Materials today. Bio · 2026Review
- Role of the stromal and immune microenvironment in intrahepatic cholangiocarcinoma.JHEP reports : innovation in hepatology · 2026Review
- Engineered Lipid Nanoparticles with Promoted Endosomal Escape and R283S-Mediated Stimulator of Interferon Genes (STING) Activation for Pancreatic Cancer Immunotherapy.Pharmaceutics · 2026Article
- The Conflicting Role of Myeloid Cells in CAR T-Cell Therapy.Cancer research · 2026Review
- Radiotherapy as a partner for immunotherapy in pancreatic cancer: current landscape and future directions.Frontiers in oncology · 2026Review
- Emerging Chimeric Antigen Receptor-Immune Cell Therapy for Pancreatic Cancer: Mechanisms, Clinical Advances, and Future Perspectives.Oncology research · 2026Review
- CAR T cell cancer immunotherapy: who does the job?Frontiers in immunology · 2026Review
- Myeloid-Derived Suppressor Cells and Radiotherapy: Regulation and Clinical Implications.Journal of Cancer · 2026Review
- Next-generation CAR-T cells design: leveraging tumor features for enhanced efficacy.Molecular cancer · 2025Review
- Harnessing the power of cancer-associated fibroblasts to revolutionize pancreatic cancer treatment.Cancer biology & medicine · 2025Review
- CAR-Macrophage Cell Therapy: A New Era of Hope for Pancreatic Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Review
- Review
- CAR T cell therapies in gastrointestinal cancers: current clinical trials and strategies to overcome challenges.Nature reviews. Gastroenterology & hepatology · 2025Review
- Pitfalls and strategies of CAR-T therapy in solid tumors and implications for chordoma treatment.Immunotherapy · 2025Review
- Strategies to overcome tumour relapse caused by antigen escape after CAR T therapy.Molecular cancer · 2025Review
- Beyond the blood: expanding CAR T cell therapy to solid tumors.Nature biotechnology · 2025Review
- Review
Corrections and comments
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Authors and funding
13 authors.
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Abstract
Pancreatic ductal adenocarcinoma (PDAC) represents a challenge in oncology, with limited treatment options for advanced-stage patients. Chimeric antigen receptor T cell (CAR T) therapy targeting mesothelin (MSLN) shows promise, but challenges such as the hostile immunosuppressive tumor microenvironment (TME) hinder its efficacy. This study explores the synergistic potential of combining proton radiation therapy (RT) with MSLN-targeting CAR T therapy in a syngeneic PDAC model. Proton RT significantly increased MSLN expression in tumor cells and caused a significant increase in CAR T cell infiltration into tumors. The combination therapy reshaped the immunosuppressive TME, promoting antitumorigenic M1 polarized macrophages and reducing myeloid-derived suppressor cells (MDSC). In a flank PDAC model, the combination therapy demonstrated superior attenuation of tumor growth and improved survival compared to individual treatments alone. In an orthotopic PDAC model treated with image-guided proton RT, tumor growth was significantly reduced in the combination group compared to the RT treatment alone. Further, the combination therapy induced an abscopal effect in a dual-flank tumor model, with increased serum interferon-γ levels and enhanced proliferation of extratumoral CAR T cells. In conclusion, combining proton RT with MSLN-targeting CAR T therapy proves effective in modulating the TME, enhancing CAR T cell trafficking, and exerting systemic antitumor effects. Thus, this combinatorial approach could present a promising strategy for improving outcomes in unresectable PDAC.
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