CD200AR-L

P1, N=24, Recruiting, OX2 Therapeutics

This also facilitated the priming of anti-tumor T cell responses, which could be further exploited using immune checkpoint blockade with the CD200 activation receptor ligand (CD200AR-L) peptide. Our findings here are significant in that they offer the possibility to develop oncolytic viruses as highly specific, escape-targeting viro-immunotherapeutic agents to be used in conjunction with recurrence of tumors following multiple different types of frontline cancer therapies.

No abstract available

CD200AR-L is administered on days 1 and 2 by suprascapular intradermal injection following the application of topical imiquimod. Patients are monitored for adverse events, including immune-mediated intracranial edema and other immune-related complications, and their neurological function is scored per NANO criteria. Correlative studies include immune monitoring (including expression of CD200R1, PD1/PD-L1, and CTLA-4) and MRI imaging assessment per iRANO criteria.

This therapy consists of an alternative checkpoint inhibitor peptide (CD200AR-L) that modulates the CD200 immune checkpoint, currently being used in an adult phase I safety trial for recurrent glioblastoma trial (NCT04642937) and a canine high-grade spontaneous glioma trial (U01CA224160-01)...These data showed that peripheral immune cell phenotypes were linked to the outcome of the immunotherapy, thus dogs with better immune cell profiles, including increased cytotoxic differentiation, had a better prognosis and longer overall survival rates. Taken together, these results suggest that variation in patient responsiveness can be explained by differences in peripheral immune cell proliferation and differentiation soon after the initiation of immunotherapy.

METHODS Single-center, first-in-human, dose-escalation phase 1 clinical trial (NCT04642937) utilizing a 3 + 3 design initiated accrual in 12/2020 at dose level-1; CD200AR-L 3.75micrograms/kg/dose administered on days 1 and 2 by intradermal injection after topical imiquimod...RESULTS Between 12/2020 to 3/2021, 6 patients were enrolled on dose level-1; aged 37-65 years, 4 men, all with KPS >/= 80, and 3 patients on daily dexamethasone (4mg (n=2), 2mg (n=1))...IrICE symptoms were temporarily mitigated with ‘bevacizumab rescue protocol.’ No patients had local injection site reactions...CONCLUSION Initial dosing of CD200AR-L was well tolerated with early positive signal of immunological effect. Enrollment continues, now at dose level-2; CD200AR-L at 5micrograms/kg/dose.

When we combined CD200AR-L with an immune-stimulatory gene therapy, in an intracranial GBM model in vivo, we observed increased median survival, and long-term survivors. These studies are the first to characterize the signaling pathway used by the CD200AR, demonstrating a novel strategy for modulating immune checkpoints for immunotherapy currently being analyzed in a phase I adult trial.