Treatment combining CD200 immune checkpoint inhibitor and tumor-lysate vaccination after surgery for pet dogs with high-grade glioma

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Abstract

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.

Original languageEnglish (US)
Article number137
JournalCancers
Volume11
Issue number2
DOIs
StatePublished - Jan 1 2019

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Pets
Glioma
Vaccination
Dogs
Antigen-Presenting Cells
Glioblastoma
Peptides
Canidae
T-Lymphocytes
Neoplasms
Cancer Vaccines
Proteins
Tumor Microenvironment
Immunosuppressive Agents
Immunotherapy
Therapeutics
Ligands
Injections

Keywords

  • Dogs
  • Glioma
  • Immunotherapy
  • Tumor lysate

PubMed: MeSH publication types

  • Journal Article

Cite this

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title = "Treatment combining CD200 immune checkpoint inhibitor and tumor-lysate vaccination after surgery for pet dogs with high-grade glioma",
abstract = "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.",
keywords = "Dogs, Glioma, Immunotherapy, Tumor lysate",
author = "Olin, {Michael R.} and Elisabet Ampudia-Mesias and Pennell, {Christopher A.} and Aaron Sarver and Chen, {Clark C.} and Moertel, {Christopher L.} and Hunt, {Matthew A.} and Pluhar, {G. Elizabeth}",
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AU - Olin, Michael R.

AU - Ampudia-Mesias, Elisabet

AU - Pennell, Christopher A.

AU - Sarver, Aaron

AU - Chen, Clark C.

AU - Moertel, Christopher L.

AU - Hunt, Matthew A.

AU - Pluhar, G. Elizabeth

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N2 - 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.

AB - 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.

KW - Dogs

KW - Glioma

KW - Immunotherapy

KW - Tumor lysate

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