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Low-dose X-ray radiotherapy-radiodynamic therapy via nanoscale metal-organic frameworks enhances checkpoint blockade immunotherapy.
Lu, Kuangda; He, Chunbai; Guo, Nining; Chan, Christina; Ni, Kaiyuan; Lan, Guangxu; Tang, Haidong; Pelizzari, Charles; Fu, Yang-Xin; Spiotto, Michael T; Weichselbaum, Ralph R; Lin, Wenbin.
Afiliación
  • Lu K; Department of Chemistry, The University of Chicago, Chicago, IL, USA.
  • He C; Department of Chemistry, The University of Chicago, Chicago, IL, USA.
  • Guo N; Department of Chemistry, The University of Chicago, Chicago, IL, USA.
  • Chan C; The Ludwig Center for Metastasis Research, The University of Chicago, Chicago, IL, USA.
  • Ni K; Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, IL, USA.
  • Lan G; Department of Chemistry, The University of Chicago, Chicago, IL, USA.
  • Tang H; Department of Chemistry, The University of Chicago, Chicago, IL, USA.
  • Pelizzari C; Department of Chemistry, The University of Chicago, Chicago, IL, USA.
  • Fu YX; Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Spiotto MT; Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, IL, USA.
  • Weichselbaum RR; Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • Lin W; Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, IL, USA.
Nat Biomed Eng ; 2(8): 600-610, 2018 08.
Article en En | MEDLINE | ID: mdl-31015630
Checkpoint blockade immunotherapy relies on energized cytotoxic T cells attacking tumour tissue systemically. However, for many cancers, the reliance on T cell infiltration leads to low response rates. Conversely, radiotherapy has served as a powerful therapy for local tumours over the past 100 years, yet is rarely sufficient to cause systemic tumour rejection. Here, we describe a treatment strategy that combines nanoscale metal-organic framework (nMOF)-enabled radiotherapy-radiodynamic therapy with checkpoint blockade immunotherapy for both local and systemic tumour elimination. In mouse models of breast and colorectal cancer, intratumorally injected nMOFs treated with low doses of X-ray irradiation led to the eradication of local tumours and, when loaded with an inhibitor of the immune checkpoint molecule indoleamine 2,3-dioxygenase, the irradiated nMOFs led to consistent abscopal responses that rejected distal tumours. By combining the advantages of local radiotherapy and systemic tumour rejection via synergistic X-ray-induced in situ vaccination and indoleamine 2,3-dioxygenase inhibition, nMOFs may overcome some of the limitations of checkpoint blockade in cancer treatment.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Terapia por Rayos X / Nanoestructuras / Estructuras Metalorgánicas / Inmunoterapia Límite: Animals / Humans Idioma: En Revista: Nat Biomed Eng Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Terapia por Rayos X / Nanoestructuras / Estructuras Metalorgánicas / Inmunoterapia Límite: Animals / Humans Idioma: En Revista: Nat Biomed Eng Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido