Immune Checkpoint-Bioengineered Beta Cell Vaccine Reverses Early-Onset Type 1 Diabetes

Kin Man Au, Yusra Medik, Qi Ke, Roland Tisch, Andrew Z. Wang

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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.

Original languageEnglish (US)
Article number2101253
JournalAdvanced Materials
Volume33
Issue number25
DOIs
StatePublished - Jun 24 2021
Externally publishedYes

Keywords

  • bioorthogonal click chemistry
  • dendrimers
  • extracellular matrix
  • immune checkpoint
  • metabolic glycoengineering
  • type 1 diabetes

ASJC Scopus subject areas

  • Materials Science(all)
  • Mechanics of Materials
  • Mechanical Engineering

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