Pediatric Oncology and Clinical Pediatrics

Biography

Biography: Michael Olin

Abstract

Despite the extensive use of tumor-derived vaccines for treatment of CNS tumors, the suppressive tumor-bound protein CD200 has been overlooked to date. CD200 is highly expressed in a variety of human tumors. Our preliminary studies detected CD200 on multiple CNS tumors. This introduces a major problem for the development of tumor-based cancer vaccines. We are “shooting ourselves in the foot” by vaccinating patients with cancer vaccines designed to mount an anti-tumor response. CD200 acts as a checkpoint blockade when engaging its receptor CD200R. CD200 upregulates peptidylprolyl isomerase A (PPIA), resulting in immune suppression. CD200 is expressed on endothelial cells within CNS tumor vessels down-regulating T-cell activation. We have developed a competitive inhibitor peptide overcoming CD200-induced immunosuppression. CD200 inhibitor peptide inhibits PPIA upregulation, enhances cytokine production, and significantly enhances survival. In addition, the CD200 inhibitor results in tumor regression and enhanced survival benefit in our canine model. Impact: We are the first to correlate CD200 in brain tumors and tumor-derived vaccines as an inhibitor of immune activation. Our data suggest that we are suppressing the immune system with the same vaccines designed specifically to induce an anti-tumor response. Tumor endothelial expression of CD200 is also a likely reason for escape from native immune surveillance and failure of other immunotherapeutic approaches. We are optimistic that use of our competitive inhibitor peptide against CD200 and anti-CD200R antibody will ultimately lead to the development of novel therapeutics that improve the efficacy of cancer immunotherapy.