A nanoscale metal organic frameworks-based vaccine synergises with PD-1 blockade to potentiate anti-tumour immunity

Xia Li; Xiupeng Wang; Atsuo Ito; Noriko M Tsuji

doi:10.1038/s41467-020-17637-z

A nanoscale metal organic frameworks-based vaccine synergises with PD-1 blockade to potentiate anti-tumour immunity

Nat Commun. 2020 Jul 31;11(1):3858. doi: 10.1038/s41467-020-17637-z.

Authors

Xia Li¹, Xiupeng Wang², Atsuo Ito¹, Noriko M Tsuji³

Affiliations

¹ Department of Life Science and Biotechnology, Health and Medical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Central 6, 1-1-1 Higashi, Tsukuba, Ibaraki, 305-8566, Japan.
² Department of Life Science and Biotechnology, Health and Medical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Central 6, 1-1-1 Higashi, Tsukuba, Ibaraki, 305-8566, Japan. xp-wang@aist.go.jp.
³ Department of Life Science and Biotechnology, Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Central 6, 1-1-1 Higashi, Tsukuba, Ibaraki, 305-8566, Japan.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibodies, Neutralizing / pharmacology*
Antigens, Neoplasm / administration & dosage
Antigens, Neoplasm / immunology
CD8-Positive T-Lymphocytes / drug effects
CD8-Positive T-Lymphocytes / immunology
Cancer Vaccines / chemistry
Cancer Vaccines / pharmacology*
Cytotoxicity, Immunologic
Drug Compounding
Female
Humans
Immunity, Innate / drug effects
Immunotherapy / methods
Lymph Nodes / drug effects
Lymph Nodes / immunology
Lymphoma / immunology
Lymphoma / mortality
Lymphoma / pathology
Lymphoma / therapy*
Metal-Organic Frameworks / chemical synthesis
Metal-Organic Frameworks / pharmacology*
Mice
Mice, Inbred C57BL
Nanoparticles / administration & dosage*
Nanoparticles / chemistry
Ovalbumin / administration & dosage
Ovalbumin / immunology
Programmed Cell Death 1 Receptor / antagonists & inhibitors*
Programmed Cell Death 1 Receptor / immunology
Silicon Dioxide / chemistry
Survival Analysis
Tumor Burden / drug effects
Xenograft Model Antitumor Assays

Substances

Antibodies, Neutralizing
Antigens, Neoplasm
Cancer Vaccines
Metal-Organic Frameworks
PDCD1 protein, human
Programmed Cell Death 1 Receptor
Silicon Dioxide
Ovalbumin