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Cancers 2019, 11(2), 137; https://doi.org/10.3390/cancers11020137

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

1
Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA
2
Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA
3
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA
4
Institute for Health Informatics, University of Minnesota, Minneapolis, MN 55455, USA
5
Department of Neurosurgery, University of Minnesota, Minneapolis, MN 55455, USA
6
Department of Veterinary Clinical Sciences, University of Minnesota, St. Paul, MN 55108, USA;
*
Author to whom correspondence should be addressed.
Received: 3 December 2018 / Revised: 14 January 2019 / Accepted: 15 January 2019 / Published: 24 January 2019
(This article belongs to the Special Issue Cancer Vaccines: Research and Applications)
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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. View Full-Text
Keywords: glioma; immunotherapy; tumor lysate; dogs glioma; immunotherapy; tumor lysate; dogs
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Olin, M.R.; Ampudia-Mesias, E.; Pennell, C.A.; Sarver, A.; Chen, C.C.; Moertel, C.L.; Hunt, M.A.; Pluhar, G.E. Treatment Combining CD200 Immune Checkpoint Inhibitor and Tumor-Lysate Vaccination after Surgery for Pet Dogs with High-Grade Glioma. Cancers 2019, 11, 137.

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