IMMU-03. TARGETING THE CD200 CHECKPOINT BLOCKADE FOR THE FIGHT AGAINST CENTRAL NERVOUS SYSTEM TUMORS

Abstract Glioblastoma multiforme is an incurable primary brain tumor. To address this dismal outcome, aggressive interventions need to be pursued. Recently, the FDA approved immune checkpoint inhibitor therapy for solid tumors that are otherwise refractory to standard therapy heralding a new era for effectively treating cancer. Yet, immune checkpoint inhibitors yield poor responses for patients with glioblastoma, calling into question whether cancer immunotherapy can be applied to glioblastoma. We are targeting an alternative checkpoint blockade. The CD200 checkpoint blockade is a paired inhibitory and activation receptors. Targeting these receptors activate antigen presenting cells enhancing dendritic cell maturation, cytokine production and antigen specific T cell activation, which significantly extend survival in two murine glioma models. In addition, in an ongoing pilot study using dogs diagnosed with high-grade glioma, patients receiving a canine specific CD200 peptide inhibitor in combination with the autologous tumor lysate vaccine had enhanced survival past 820 days, relative to 214 days with lysate alone Currently, 25% of the dogs are alive past 810 days post-surgery. Death due to tumor recurrence was observed in 8 dogs (40%); 6 dogs (30%) died of non-tumor related deaths. In contrast, 100% of the dogs in the tumor-lysate-only group died of tumor recurrence. Furthermore, serum chemistry profiles showed that the peptide did not induce any systemic toxicity. Importantly, we developed human CD200 inhibitors demonstrating strong immune responses. Our humanized inhibitors activate CD14 cells, and enhances cytokine secretion, enhance dendritic cell maturation enhances, and antigen-specific immune responses.