Journal
CHEM
Volume 5, Issue 7, Pages 1892-1913Publisher
CELL PRESS
DOI: 10.1016/j.chempr.2019.05.013
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Funding
- National Cancer Institute [U01-CA198989, 1R01CA216436]
- University of Chicago Medicine Comprehensive Cancer Center [NIH CCSG: P30 CA014599]
- Ludwig Institute for Metastasis Research
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Checkpoint blockade immunotherapy (CBI) elicits durable therapeutic responses by blocking T cell inhibitory pathways of tumors with pre-infiltrated T cells and/or high mutational burden to activate antitumor immunity but is ineffective against poorly immunogenic tumors. Immunogenic radiotherapy, photodynamic therapy (PDT), and chemotherapy have thus been examined as immunomodulatory adjuvants to augment CBI. Dysregulated hormone production has long been linked to tumorigenesis and poor prognosis of various cancers. Herein, we report the use of a Cu-porphyrin nanoscale metal-organic framework (nMOF) to mediate synergistic hormone-triggered chemodynamic therapy (CDT) and light-triggered PDT. The combination of CDT- and PDT-based radical therapy with a programmed cell death ligand 1 blockade effectively extends the local therapeutic effects of CDT and PDT to distant tumors via abscopal effects on mouse tumor models with high levels of estradiol. Our work thus establishes the feasibility of combining nMOF-mediated radical therapy with CBI to elicit systemic antitumor immunity in hormonally dysregulated tumor phenotypes.
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