Cargando…
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...
Autores principales: | , , , , , , , |
---|---|
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 |
_version_ | 1783401383188234240 |
---|---|
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. |
format | Online Article Text |
id | pubmed-6406711 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT olinmichaelr treatmentcombiningcd200immunecheckpointinhibitorandtumorlysatevaccinationaftersurgeryforpetdogswithhighgradeglioma AT ampudiamesiaselisabet treatmentcombiningcd200immunecheckpointinhibitorandtumorlysatevaccinationaftersurgeryforpetdogswithhighgradeglioma AT pennellchristophera treatmentcombiningcd200immunecheckpointinhibitorandtumorlysatevaccinationaftersurgeryforpetdogswithhighgradeglioma AT sarveraaron treatmentcombiningcd200immunecheckpointinhibitorandtumorlysatevaccinationaftersurgeryforpetdogswithhighgradeglioma AT chenclarkc treatmentcombiningcd200immunecheckpointinhibitorandtumorlysatevaccinationaftersurgeryforpetdogswithhighgradeglioma AT moertelchristopherl treatmentcombiningcd200immunecheckpointinhibitorandtumorlysatevaccinationaftersurgeryforpetdogswithhighgradeglioma AT huntmatthewa treatmentcombiningcd200immunecheckpointinhibitorandtumorlysatevaccinationaftersurgeryforpetdogswithhighgradeglioma AT pluhargelizabeth treatmentcombiningcd200immunecheckpointinhibitorandtumorlysatevaccinationaftersurgeryforpetdogswithhighgradeglioma |