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

Cancers

ClarkC. Chen¹  MatthewA. Hunt¹  MichaelR. Olin²  Elisabet Ampudia-Mesias²  ChristopherL. Moertel²  ChristopherA. Pennell³  Aaron Sarver³  G.Elizabeth Pluhar³ 

[1] Department of Neurosurgery, University of Minnesota, Minneapolis, MN 55455, USA;Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA;Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA;

关键词: glioma;    immunotherapy;    tumor lysate;    dogs;   

DOI  :  10.3390/cancers11020137

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown