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

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.

• Authors: 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
• Journal: Science advances (Sci Adv) Vol. 6 Issue 35 Pg. eaba5573 (08 2020) ISSN: 2375-2548 [Electronic] United States
• PMID: 32923626 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

Chemical References

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

Topics

• 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