Immunotherapy via PD-L1-presenting biomaterials leads to long-term islet graft survival. 2020

María M Coronel, and Karen E Martin, and Michael D Hunckler, and Graham Barber, and Eric B O'Neill, and Juan D Medina, and Enrico Opri, and Claire A McClain, and Lalit Batra, and Jessica D Weaver, and Hong S Lim, and Peng Qiu, and Edward A Botchwey, and Esma S Yolcu, and Haval Shirwan, and Andrés J García
Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, USA.

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.

UI MeSH Term Description Entries
D007155 Immunologic Factors Biologically active substances whose activities affect or play a role in the functioning of the immune system. Biological Response Modifier,Biomodulator,Immune Factor,Immunological Factor,Immunomodulator,Immunomodulators,Biological Response Modifiers,Biomodulators,Factors, Immunologic,Immune Factors,Immunological Factors,Modifiers, Biological Response,Response Modifiers, Biological,Factor, Immune,Factor, Immunological,Factors, Immune,Factors, Immunological,Modifier, Biological Response,Response Modifier, Biological
D007167 Immunotherapy Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. Immunotherapies
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D006085 Graft Survival The survival of a graft in a host, the factors responsible for the survival and the changes occurring within the graft during growth in the host. Graft Survivals,Survival, Graft,Survivals, Graft
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001672 Biocompatible Materials Synthetic or natural materials, other than DRUGS, that are used to replace or repair any body TISSUES or bodily function. Biomaterials,Bioartificial Materials,Hemocompatible Materials,Bioartificial Material,Biocompatible Material,Biomaterial,Hemocompatible Material,Material, Bioartificial,Material, Biocompatible,Material, Hemocompatible
D016381 Islets of Langerhans Transplantation The transference of pancreatic islets within an individual, between individuals of the same species, or between individuals of different species. Grafting, Islets of Langerhans,Pancreatic Islets Transplantation,Transplantation, Islets of Langerhans,Transplantation, Pancreatic Islets,Islands of Langerhans Transplantation,Islands of Pancreas Transplantation,Islet Transplantation,Transplantation, Islands of Langerhans,Transplantation, Islands of Pancreas,Transplantation, Islet,Islet Transplantations,Islets Transplantation, Pancreatic,Transplantations, Islet
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D060890 B7-H1 Antigen An inhibitory B7 antigen that contains V-type and C2 type immunoglobulin domains. It has specificity for the T-CELL receptor PROGRAMMED CELL DEATH 1 PROTEIN and provides negative signals that control and inhibit T-cell responses. It is found at higher than normal levels on tumor cells, suggesting its potential role in TUMOR IMMUNE EVASION. Antigens, CD274,PD-L1 Protein,Programmed Cell Death 1 Ligand 1 Protein,Programmed Death Ligand 1,B7-H1 Immune Costimulatory Protein,B7H1 Immune Costimulatory Protein,CD274 Antigen,PD-L1 Costimulatory Protein,Programmed Cell Death 1 Ligand 1,Antigen, B7-H1,Antigen, CD274,B7 H1 Antigen,B7 H1 Immune Costimulatory Protein,CD274 Antigens,Costimulatory Protein, PD-L1,PD L1 Costimulatory Protein,PD L1 Protein
D061026 Programmed Cell Death 1 Receptor An inhibitory T-lymphocyte receptor that has specificity for CD274 ANTIGEN and PROGRAMMED CELL DEATH 1 LIGAND 2 PROTEIN. Signaling by the receptor limits T cell proliferation and INTERFERON GAMMA synthesis. The receptor also may play an essential role in the regulatory pathway that induces PERIPHERAL TOLERANCE. PD-1 Protein,Programmed Cell Death 1 Protein,Programmed Cell Death Protein 1,Antigens, CD279,CD279 Antigen,PD-1 Receptor,PD1 Receptor,Antigen, CD279,CD279 Antigens,PD 1 Protein,PD 1 Receptor,Receptor, PD-1,Receptor, PD1

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