Department of Chemistry, University of Chicago, Chicago, IL 60637, USA.
Department of Radiation and Cellular Oncology and the Ludwig Center for Metastasis Research, University of Chicago, Chicago, IL 60637, USA.
Sci Adv. 2020 Oct 2;6(40). doi: 10.1126/sciadv.abb5223. Print 2020 Oct.
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.
癌症疫苗一直被积极研究以增强抗肿瘤免疫。在这里，我们设计了纳米级金属有机框架（nMOFs）作为局部激活的免疫疗法，以释放危险相关分子模式（DAMPs）和肿瘤抗原，并递送病原体相关分子模式（PAMPs）用于原位个性化癌症疫苗接种。当被 X 射线激活时，nMOFs 可有效产生活性氧以释放 DAMPs 和肿瘤抗原，同时递送 CpG 寡脱氧核苷酸作为 PAMPs 以促进抗原呈递细胞的成熟。总之，DAMPs、肿瘤抗原和 PAMPs 在肿瘤引流淋巴结中扩增细胞毒性 T 细胞，以重新激活适应性免疫系统以实现局部肿瘤消退。当与免疫检查点抑制剂联合治疗时，nMOF 基疫苗的局部治疗效果通过减轻 T 细胞耗竭而扩展到远处肿瘤。我们的工作证明了 nMOFs 作为 X 射线激活的原位癌症疫苗的潜力，可唤醒宿主的先天和适应性免疫系统以实现全身抗肿瘤免疫。
