Nanoscale metal-organic frameworks enhance radiotherapy to potentiate checkpoint blockade immunotherapy

Kaiyuan Ni, Guangxu Lan, Christina Chan, Bryan Quigley, Kuangda Lu, Theint Aung, Nining Guo, Patrick Riviere, Ralph R. Weichselbaum and Wenbin Lin ()
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Kaiyuan Ni: The University of Chicago
Guangxu Lan: The University of Chicago
Christina Chan: The University of Chicago
Bryan Quigley: The University of Chicago
Kuangda Lu: The University of Chicago
Theint Aung: The University of Chicago
Nining Guo: The University of Chicago
Patrick Riviere: The University of Chicago
Ralph R. Weichselbaum: The University of Chicago
Wenbin Lin: The University of Chicago

Nature Communications, 2018, vol. 9, issue 1, 1-12

Abstract: Abstract Checkpoint blockade immunotherapy enhances systemic antitumor immune response by targeting T cell inhibitory pathways; however, inadequate T cell infiltration has limited its anticancer efficacy. Radiotherapy (RT) has local immunomodulatory effects that can alter the microenvironment of irradiated tumors to synergize with immune checkpoint blockade. However, even with high doses of radiation, RT has rarely elicited systemic immune responses. Herein, we report the design of two porous Hf-based nanoscale metal-organic frameworks (nMOFs) as highly effective radioenhancers that significantly outperform HfO2, a clinically investigated radioenhancer in vitro and in vivo. Importantly, the combination of nMOF-mediated low-dose RT with an anti-programmed death-ligand 1 antibody effectively extends the local therapeutic effects of RT to distant tumors via abscopal effects. Our work establishes the feasibility of combining nMOF-mediated RT with immune checkpoint blockade to elicit systemic antitumor immunity in non-T cell-inflamed tumor phenotypes without normal tissue toxicity, promising to broaden the application of checkpoint blockade immunotherapy.

Date: 2018
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DOI: 10.1038/s41467-018-04703-w

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