Low-dose X-ray radiotherapy–radiodynamic therapy via nanoscale metal–organic frameworks enhances checkpoint blockade immunotherapy

Kuangda Lu, Chunbai He, Nining Guo, Christina Chan, Kaiyuan Ni, Guangxu Lan, Haidong Tang, Charles Pelizzari, Yang Xin Fu, Michael T. Spiotto, Ralph R. Weichselbaum, Wenbin Lin

Research output: Contribution to journalArticle

114 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1-11
Number of pages11
JournalNature Biomedical Engineering
DOIs
StateAccepted/In press - Mar 26 2018

ASJC Scopus subject areas

  • Biomedical Engineering
  • Biotechnology
  • Bioengineering
  • Medicine (miscellaneous)
  • Computer Science Applications

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    Lu, K., He, C., Guo, N., Chan, C., Ni, K., Lan, G., Tang, H., Pelizzari, C., Fu, Y. X., Spiotto, M. T., Weichselbaum, R. R., & Lin, W. (Accepted/In press). Low-dose X-ray radiotherapy–radiodynamic therapy via nanoscale metal–organic frameworks enhances checkpoint blockade immunotherapy. Nature Biomedical Engineering, 1-11. https://doi.org/10.1038/s41551-018-0203-4