封锁
免疫系统
免疫增强剂
免疫疗法
癌症研究
免疫
癌症免疫疗法
医学
免疫检查点
免疫学
受体
内科学
作者
Xia Li,Xiupeng Wang,Atsuo Ito,Noriko M. Tsuji
标识
DOI:10.1038/s41467-020-17637-z
摘要
Abstract Checkpoint blockade therapy has provided noteworthy benefits in multiple cancers in recent years; however, its clinical benefits remain confined to 10–40% of patients with extremely high costs. Here, we design an ultrafast, low-temperature, and universal self-assembly route to integrate immunology-associated large molecules into metal-organic-framework (MOF)-gated mesoporous silica (MS) as cancer vaccines. Core MS nanoparticles, acting as an intrinsic immunopotentiator, provide the niche, void, and space to accommodate antigens, soluble immunopotentiators, and so on, whereas the MOF gatekeeper protects the interiors from robust and off-target release. A combination of MOF-gated MS cancer vaccines with systemic programmed cell death 1 (PD-1) blockade therapy generates synergistic effects that potentiate antitumour immunity and reduce the effective dose of an anti-PD-1 antibody to as low as 1/10 of that for PD-1 blockade monotherapy in E.G7-OVA tumour-bearing mice, with eliciting the robust adaptive OVA-specific CD8 + T-cell responses, reversing the immunosuppressive pathway and inducing durable tumour suppression.
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