@article{d60c42a33f4e481b989887f580b7d52f,
title = "Immune Checkpoint-Bioengineered Beta Cell Vaccine Reverses Early-Onset Type 1 Diabetes",
abstract = "Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease that results from autoreactive T cells destroying insulin-producing pancreatic beta (β) cells. The development of T1DM is associated with the deficiency of co-inhibitory immune checkpoint ligands (e.g., PD-L1, CD86, and Gal-9) in β cells. Here, a new translational approach based on metabolic glycoengineering and bioorthogonal click chemistry, which bioengineers β cells with co-inhibitory immune checkpoint molecules that induce antigen-specific immunotolerance and reverse early-onset hyperglycemia is reported. To achieve this goal, a subcutaneous injectable acellular pancreatic extracellular matrix platform for localizing the bioengineered β cells while creating a pancreas-like immunogenic microenvironment, in which the autoreactive T cells can interface with the β cells, is devised.",
keywords = "bioorthogonal click chemistry, dendrimers, extracellular matrix, immune checkpoint, metabolic glycoengineering, type 1 diabetes",
author = "Au, {Kin Man} and Yusra Medik and Qi Ke and Roland Tisch and Wang, {Andrew Z.}",
note = "Funding Information: The authors thank the Microscopy Service Laboratory Core, Animal Study Core, Small Animal Imaging Facility, Animal Clinical Laboratory, Animal Histopathology Core Facility, Translation Pathology Lab, UNC Flow Cytometry Core Facility, UNC Macromolecular Interactions Facility and UNC Michael Hooker Proteomics Centre in the School of Medicine, and Chapel Hill Analytical and Nanofabrication Laboratory (CHANL) at the University of North Carolina at Chapel Hill for their assistance with procedures in this manuscript. UNC Lineberger Animal Studies Core is supported in part by an NCI Center Core Support Grant (CA16086) to the UNC Lineberger Comprehensive Cancer Center. The UNC Flow Cytometry Core Facility was supported in part by P30CA016086 Cancer Center Core Support Grant to the UNC Lineberger Comprehensive Cancer Center. This work was supported by the University Cancer Research Fund from the University of North Carolina and R01 EB25651-01A1 grant from the National Institutes of Health/NIBIB. A.Z.W. was also supported by the National Institutes of Health Center for Nanotechnology Excellence Grant No. U54-CA151652, National Institutes of Health/NIGMS R01GM130590 and the UNC Research Opportunity Initiative. R.T. was supported by National Institutes of Health/NIAID Grant Nos. R01AI139475 and R01AI141631. Funding Information: The authors thank the Microscopy Service Laboratory Core, Animal Study Core, Small Animal Imaging Facility, Animal Clinical Laboratory, Animal Histopathology Core Facility, Translation Pathology Lab, UNC Flow Cytometry Core Facility, UNC Macromolecular Interactions Facility and UNC Michael Hooker Proteomics Centre in the School of Medicine, and Chapel Hill Analytical and Nanofabrication Laboratory (CHANL) at the University of North Carolina at Chapel Hill for their assistance with procedures in this manuscript. UNC Lineberger Animal Studies Core is supported in part by an NCI Center Core Support Grant (CA16086) to the UNC Lineberger Comprehensive Cancer Center. The UNC Flow Cytometry Core Facility was supported in part by P30CA016086 Cancer Center Core Support Grant to the UNC Lineberger Comprehensive Cancer Center. This work was supported by the University Cancer Research Fund from the University of North Carolina and R01 EB25651‐01A1 grant from the National Institutes of Health/NIBIB. A.Z.W. was also supported by the National Institutes of Health Center for Nanotechnology Excellence Grant No. U54‐CA151652, National Institutes of Health/NIGMS R01GM130590 and the UNC Research Opportunity Initiative. R.T. was supported by National Institutes of Health/NIAID Grant Nos. R01AI139475 and R01AI141631. Publisher Copyright: {\textcopyright} 2021 Wiley-VCH GmbH",
year = "2021",
month = jun,
day = "24",
doi = "10.1002/adma.202101253",
language = "English (US)",
volume = "33",
journal = "Advanced Materials",
issn = "0935-9648",
publisher = "Wiley-VCH Verlag",
number = "25",
}