Journal
SCIENCE ADVANCES
Volume 6, Issue 40, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abb5223
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Funding
- National Cancer Institute [U01-CA198989, 1R01CA253655]
- Department of Defense [PC170934P2]
- University of Chicago Medicine Comprehensive Cancer Center [NIH CCSG: P30 CA014599]
- Ludwig Institute for Metastasis Research
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Cancer vaccines have been actively pursued to bolster antitumor immunity. Here, we designed nanoscale metal-organic frameworks (nMOFs) as locally activable immunotherapeutics to release danger-associated molecular patterns (DAMPs) and tumor antigens and deliver pathogen-associated molecular patterns (PAMPs) for in situ personalized cancer vaccination. When activated by x-rays, nMOFs effectively generate reactive oxygen species to release DAMPs and tumor antigens while delivering CpG oligodeoxynucleotides as PAMPs to facilitate the maturation of antigen-presenting cells. Together, DAMPs, tumor antigens, and PAMPs expand cytotoxic T cells in tumor-draining lymph nodes to reinvigorate the adaptive immune system for local tumor regression. When treated in combination with an immune checkpoint inhibitor, the local therapeutic effects of nMOF-based vaccines were extended to distant tumors via attenuating T cell exhaustion. Our work demonstrates the potential of nMOFs as x-ray-activable in situ cancer vaccines to awaken the host's innate and adaptive immune systems for systemic antitumor immunity.
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