학술논문

Treatment Combining CD200 Immune Checkpoint Inhibitor and Tumor-Lysate Vaccination after Surgery for Pet Dogs with High-Grade Glioma.
Document Type
Article
Source
Cancers. Feb2019, Vol. 11 Issue 2, p137. 1p.
Subject
*IMMUNOSUPPRESSIVE agents
*ANIMAL experimentation
*ANTIGEN presenting cells
*CELL physiology
*COMBINATION drug therapy
*DOGS
*GLIOMAS
*IMMUNIZATION
*IMMUNOTHERAPY
*PEPTIDES
*PETS
*T cells
*CANCER vaccines
*MEMBRANE glycoproteins
*CHEMICAL inhibitors
Language
ISSN
2072-6694
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. [ABSTRACT FROM AUTHOR]