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

María M. Coronel, Karen E. Martin, Michael D. Hunckler, Graham Barber, Eric B. O'Neill, Juan D. Medina, Enrico Opri, Claire A. McClain, Lalit Batra, Jessica D. Weaver, Hong S. Lim, Peng Qiu, Edward A. Botchwey, Esma S. Yolcu, Haval Shirwan, Andrés J. García

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbereaba5573
JournalScience Advances
Volume6
Issue number35
DOIs
StatePublished - Aug 2020

ASJC Scopus subject areas

  • General

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