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

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10 Scopus citations

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

Bibliographical note

Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.

Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.

Keywords

  • Dogs
  • Glioma
  • Immunotherapy
  • Tumor lysate

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