sMIC Suppresses the Immune System in Cancer Patients
Early in cancer development, human cancer cells express MIC on their cell surface in response to stress or oncogenic insult. Surface MIC acts as a ligand for the NKG2D immunoreceptor, which activates natural killer cells and co-stimulates CD8+ cytolytic T cells, leading to detection and elimination of tumor cells as part of normal immune surveillance activities. As the cancer progresses, cancer cells cleave surface MIC and releases a soluble form of MIC (sMIC) into the circulation. sMIC is highly immunosuppressive and disables the immune system by impairing NK and T cell activity, expanding the population of myeloid-derived suppressor cells and tumor-associated macrophages in tumor microenvironment. Altogether, these damaging effects of sMIC allows cancer cells to grow and thrive. CuraB-10 clears the immune destruction of sMIC and re-invigorates the immune system to fight cancer (Figure 1)
The Biology of CuraB10 Technology
In preclinical animal studies, CuraB-10 monotherapy improved survival, shrank primary tumors, and eliminated metastasis by up to 90%, even in tumors that are non-responsive to immune checkpoint inhibitors. When used in combination, CuraB-10 remarkably enhances tumor response to immune checkpoint inhibitors (Figure 2)
CuraB-10 single agent is effective in tumors that are non-responsive to immune checkpoint inhibitors (ICI) and synergizes with ICI when combined.
Over 80% of human tumors release sMIC. Patients with metastatic tumors have elevated serum sMIC. CuraB-10 can have indications in all sMIC-positive cancer patients. Serum circulation sMIC can be used as companion biomarker for patient selection.