T lymphocyte membrane-decorated epigenetic nanoinducer of interferons for cancer immunotherapy

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.

Automated summary

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.