This technology is a combination immunotherapy strategy that integrates VRK2 inhibition and PD-1 blocking antibodies to enhance the efficacy of anti-tumor responses in cancer patients.
PD-1 blocking antibodies are widely used cancer immunotherapies, but clinical efficacy is limited by a short duration of response and a high percentage of non-responders. Additionally, systemic immune checkpoint inhibition can lead to significant adverse inflammatory side effects and immune-related toxicities. There is an urgent need for adjunct therapies that target specific downstream effectors in PD-1 signaling pathways to enable more selective and potent enhancement of checkpoint blockade without broadly disrupting immune tolerance.
This technology combines VRK2 kinase inhibitors with PD-1 blocking antibodies to enhance T cell-mediated anti-tumor immunity. It was demonstrated that VRK2 is required for PD-1-mediated inhibition of cytokine secretion. Pharmacological inhibition of VRK2 (using the small molecule AZD-7762) in combination with anti-PD-1 antibodies inhibits the PD-1 signaling cascade at multiple points, resulting in more robust T cell activation and improved tumor clearance compared to PD-1 blockade alone.
This technology has been validated in human primary T cells and a syngeneic mouse adenocarcinoma tumor model.
Patent Pending (US20220370408)
IR CU21245
Licensing Contact: Cynthia Lang
