TY - JOUR
T1 - Low-dose X-ray radiotherapy–radiodynamic therapy via nanoscale metal–organic frameworks enhances checkpoint blockade immunotherapy
AU - Lu, Kuangda
AU - He, Chunbai
AU - Guo, Nining
AU - Chan, Christina
AU - Ni, Kaiyuan
AU - Lan, Guangxu
AU - Tang, Haidong
AU - Pelizzari, Charles
AU - Fu, Yang Xin
AU - Spiotto, Michael T.
AU - Weichselbaum, Ralph R.
AU - Lin, Wenbin
N1 - Funding Information:
We thank C. Poon and Z. Lin for experimental help. We also thank S. J. Kron and M. S. Lesniak for kindly providing the cell lines. We acknowledge the National Cancer Institute (U01–CA198989 and R21-CA195075A), University of Chicago Medicine Comprehensive Cancer Center (NIH CCSG: P30 CA014599), Chemistry–Biology Interface training grant (NIH 5T32GM008720-15) and Ludwig Center for Metastasis Research for funding support.
Publisher Copyright:
© 2018, The Author(s).
PY - 2018/8/1
Y1 - 2018/8/1
N2 - 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.
AB - 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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U2 - 10.1038/s41551-018-0203-4
DO - 10.1038/s41551-018-0203-4
M3 - Article
C2 - 31015630
AN - SCOPUS:85044465726
SN - 2157-846X
VL - 2
SP - 600
EP - 610
JO - Nature Biomedical Engineering
JF - Nature Biomedical Engineering
IS - 8
ER -