Immunotherapy via PD-L1-presenting biomaterials leads to long-term islet graft survival

Sci Adv. 2020 Aug 28;6(35):eaba5573. doi: 10.1126/sciadv.aba5573. eCollection 2020 Aug.


Antibody-mediated immune checkpoint blockade is a transformative immunotherapy for cancer. These same mechanisms can be repurposed for the control of destructive alloreactive immune responses in the transplantation setting. Here, we implement a synthetic biomaterial platform for the local delivery of a chimeric streptavidin/programmed cell death-1 (SA-PD-L1) protein to direct "reprogramming" of local immune responses to transplanted pancreatic islets. Controlled presentation of SA-PD-L1 on the surface of poly(ethylene glycol) microgels improves local retention of the immunomodulatory agent over 3 weeks in vivo. Furthermore, local induction of allograft acceptance is achieved in a murine model of diabetes only when receiving the SA-PD-L1-presenting biomaterial in combination with a brief rapamycin treatment. Immune characterization revealed an increase in T regulatory and anergic cells after SA-PD-L1-microgel delivery, which was distinct from naïve and biomaterial alone microenvironments. Engineering the local microenvironment via biomaterial delivery of checkpoint proteins has the potential to advance cell-based therapies, avoiding the need for systemic chronic immunosuppression.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • B7-H1 Antigen* / metabolism
  • Biocompatible Materials / pharmacology
  • Graft Survival
  • Immunologic Factors
  • Immunotherapy
  • Islets of Langerhans Transplantation*
  • Mice
  • Mice, Inbred C57BL
  • Programmed Cell Death 1 Receptor
  • Streptavidin


  • B7-H1 Antigen
  • Biocompatible Materials
  • Immunologic Factors
  • Programmed Cell Death 1 Receptor
  • Streptavidin