Journal
NATURE NANOTECHNOLOGY
Volume 16, Issue 11, Pages 1271-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41565-021-00972-7
Keywords
-
Funding
- National Natural Science Foundation of China [81690265, 31870995, 81671808]
- Youth Innovation Promotion Association of CAS [2017335]
- SA-SIBS Scholarship Program
- Shandong Provincial Natural Science Foundation [ZR2019ZD25]
Ask authors/readers for more resources
Researchers have developed a novel nanoparticle platform that enhances tumor immunity while reducing immunosuppression. This platform effectively increases levels of IFNs within the tumor and inhibits tumor growth.
Impaired type I interferons (IFNs) may cause immune deficiency in tumours. Current supplementary IFN therapy partially restores anticancer immunity but simultaneously induces immune evasion by upregulating multiple immune checkpoints. Here we create a T lymphocyte membrane-decorated epigenetic nanoinducer that is engineered with programmed cell death protein 1 (PD1), which we call OPEN, for the delivery of the IFN inducer ORY-1001. OPEN increases IFNs and blocks IFN-induced immune checkpoint upregulation. OPEN also targets tumours that express programmed cell death ligand 1 (PDL1) through PDL1/PD1 recognition and subsequently triggers the internalization of OPEN and immune checkpoint proteins. OPEN, which is loaded with ORY-1001, upregulates intratumoural IFNs and downstream major histocompatibility complex I and PDL1. The replenished PDL1 enables further ligation of OPEN, which in turn blocks PDL1. These sequential processes result in an eight- and 29-fold increase of the intratumoural densities of total and active cytotoxic T lymphocytes, respectively, and a strong inhibition of xenograft tumour growth. This T lymphocyte membrane-decorated epigenetic nanoinducer presents a generalizable platform to boost antitumour immunity. Type I interferons (IFNs) have strong antitumour activity yet their clinical use is limited by their off-target toxicity and by their effect on immune evasion. Here the authors design a biomimetic nanoparticle loaded with an IFN inducer, which can at the same time replenish intratumoural IFNs and reduce their immunosuppressive activity, showing therapeutic efficacy in several animal tumour models.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available