Nanoscale metal-organic frameworks for x-ray activated in situ cancer vaccination
Kaiyuan Ni, Guangxu Lan, Nining Guo, August Culbert, Taokun Luo, Tong Wu, Ralph R. Weichselbaum, Wenbin Lin
Abstract
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.