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Treatment Combining CD200 Immune Checkpoint Inhibitor and Tumor-Lysate Vaccination after Surgery for Pet Dogs with High-Grade Glioma

Recent advances in immunotherapy have included inhibition of immune checkpoint proteins in the tumor microenvironment and tumor lysate-based vaccination strategies. We combined these approaches in pet dogs with high-grade glioma. Administration of a synthetic peptide targeting the immune checkpoint...

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Autores principales: Olin, Michael R., Ampudia-Mesias, Elisabet, Pennell, Christopher A., Sarver, Aaron, Chen, Clark C., Moertel, Christopher L., Hunt, Matthew A., Pluhar, G. Elizabeth
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6406711/
https://www.ncbi.nlm.nih.gov/pubmed/30682795
http://dx.doi.org/10.3390/cancers11020137
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author Olin, Michael R.
Ampudia-Mesias, Elisabet
Pennell, Christopher A.
Sarver, Aaron
Chen, Clark C.
Moertel, Christopher L.
Hunt, Matthew A.
Pluhar, G. Elizabeth
author_facet Olin, Michael R.
Ampudia-Mesias, Elisabet
Pennell, Christopher A.
Sarver, Aaron
Chen, Clark C.
Moertel, Christopher L.
Hunt, Matthew A.
Pluhar, G. Elizabeth
author_sort Olin, Michael R.
collection PubMed
description Recent advances in immunotherapy have included inhibition of immune checkpoint proteins in the tumor microenvironment and tumor lysate-based vaccination strategies. We combined these approaches in pet dogs with high-grade glioma. Administration of a synthetic peptide targeting the immune checkpoint protein, CD200, enhanced the capacity of antigen-presenting cells to prime T-cells to mediate an anti-glioma response. We found that in canine spontaneous gliomas, local injection of a canine-specific, CD200-directed peptide before subcutaneous delivery of an autologous tumor lysate vaccine prolonged survival relative to a historical control treated with autologous tumor lysate alone (median survivals of 12.7 months and 6.36 months, respectively). Antigen-presenting cells and T-lymphocytes primed with this peptide suppressed their expression of the inhibitory CD200 receptor, thereby enhancing their ability to initiate immune reactions in a glioblastoma microenvironment replete with the immunosuppressive CD200 protein. These results support consideration of a CD200 ligand as a novel glioblastoma immunotherapeutic agent.
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spelling pubmed-64067112019-03-21 Treatment Combining CD200 Immune Checkpoint Inhibitor and Tumor-Lysate Vaccination after Surgery for Pet Dogs with High-Grade Glioma Olin, Michael R. Ampudia-Mesias, Elisabet Pennell, Christopher A. Sarver, Aaron Chen, Clark C. Moertel, Christopher L. Hunt, Matthew A. Pluhar, G. Elizabeth Cancers (Basel) Article Recent advances in immunotherapy have included inhibition of immune checkpoint proteins in the tumor microenvironment and tumor lysate-based vaccination strategies. We combined these approaches in pet dogs with high-grade glioma. Administration of a synthetic peptide targeting the immune checkpoint protein, CD200, enhanced the capacity of antigen-presenting cells to prime T-cells to mediate an anti-glioma response. We found that in canine spontaneous gliomas, local injection of a canine-specific, CD200-directed peptide before subcutaneous delivery of an autologous tumor lysate vaccine prolonged survival relative to a historical control treated with autologous tumor lysate alone (median survivals of 12.7 months and 6.36 months, respectively). Antigen-presenting cells and T-lymphocytes primed with this peptide suppressed their expression of the inhibitory CD200 receptor, thereby enhancing their ability to initiate immune reactions in a glioblastoma microenvironment replete with the immunosuppressive CD200 protein. These results support consideration of a CD200 ligand as a novel glioblastoma immunotherapeutic agent. MDPI 2019-01-24 /pmc/articles/PMC6406711/ /pubmed/30682795 http://dx.doi.org/10.3390/cancers11020137 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Olin, Michael R.
Ampudia-Mesias, Elisabet
Pennell, Christopher A.
Sarver, Aaron
Chen, Clark C.
Moertel, Christopher L.
Hunt, Matthew A.
Pluhar, G. Elizabeth
Treatment Combining CD200 Immune Checkpoint Inhibitor and Tumor-Lysate Vaccination after Surgery for Pet Dogs with High-Grade Glioma
title Treatment Combining CD200 Immune Checkpoint Inhibitor and Tumor-Lysate Vaccination after Surgery for Pet Dogs with High-Grade Glioma
title_full Treatment Combining CD200 Immune Checkpoint Inhibitor and Tumor-Lysate Vaccination after Surgery for Pet Dogs with High-Grade Glioma
title_fullStr Treatment Combining CD200 Immune Checkpoint Inhibitor and Tumor-Lysate Vaccination after Surgery for Pet Dogs with High-Grade Glioma
title_full_unstemmed Treatment Combining CD200 Immune Checkpoint Inhibitor and Tumor-Lysate Vaccination after Surgery for Pet Dogs with High-Grade Glioma
title_short Treatment Combining CD200 Immune Checkpoint Inhibitor and Tumor-Lysate Vaccination after Surgery for Pet Dogs with High-Grade Glioma
title_sort treatment combining cd200 immune checkpoint inhibitor and tumor-lysate vaccination after surgery for pet dogs with high-grade glioma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6406711/
https://www.ncbi.nlm.nih.gov/pubmed/30682795
http://dx.doi.org/10.3390/cancers11020137
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