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         headline:T lymphocyte membrane-decorated epigenetic nanoinducer of interferons for cancer immunotherapy
         description: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.
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      headline:T lymphocyte membrane-decorated epigenetic nanoinducer of interferons for cancer immunotherapy
      description: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.
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               name:State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
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            address:
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      affiliation:
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            address:
               name:State Key Laboratory of Oncogenes and Related Genes, Renji-Med-X Stem Cell Research Center, Department of Urology, Ren Ji Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China
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      url:http://orcid.org/0000-0002-4546-0022
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            address:
               name:State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
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            name:University of Chinese Academy of Sciences
            address:
               name:University of Chinese Academy of Sciences, Beijing, China
               type:PostalAddress
            type:Organization
            name:Yantai Key Laboratory of Nanomedicine & Advanced Preparations, Yantai Institute of Materia Medica
            address:
               name:Yantai Key Laboratory of Nanomedicine & Advanced Preparations, Yantai Institute of Materia Medica, Shandong, China
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      name:Yaping Li
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      affiliation:
            name:State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences
            address:
               name:State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
               type:PostalAddress
            type:Organization
            name:University of Chinese Academy of Sciences
            address:
               name:University of Chinese Academy of Sciences, Beijing, China
               type:PostalAddress
            type:Organization
            name:Bohai Rim Advanced Research Institute for Drug Discovery
            address:
               name:Bohai Rim Advanced Research Institute for Drug Discovery, Shandong, China
               type:PostalAddress
            type:Organization
      email:[email protected]
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      name:State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
      name:University of Chinese Academy of Sciences, Beijing, China
      name:State Key Laboratory of Oncogenes and Related Genes, Renji-Med-X Stem Cell Research Center, Department of Urology, Ren Ji Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China
      name:State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
      name:University of Chinese Academy of Sciences, Beijing, China
      name:Yantai Key Laboratory of Nanomedicine & Advanced Preparations, Yantai Institute of Materia Medica, Shandong, China
      name:Yantai Key Laboratory of Nanomedicine & Advanced Preparations, Yantai Institute of Materia Medica, Shandong, China
      name:State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
      name:University of Chinese Academy of Sciences, Beijing, China
      name:State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
      name:University of Chinese Academy of Sciences, Beijing, China
      name:State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
      name:China State Institute of Pharmaceutical Industry, Shanghai, China
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      name:State Key Laboratory of Oncogenes and Related Genes, Renji-Med-X Stem Cell Research Center, Department of Urology, Ren Ji Hospital, School of Medicine and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China
      name:State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
      name:University of Chinese Academy of Sciences, Beijing, China
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      name:State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
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      name:Bohai Rim Advanced Research Institute for Drug Discovery, Shandong, China
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