An exciting development in the recent anticancer therapy field is the unprecedented success of immunotherapies that invigorate the body’s immune system in eradicating cancer cells. As cancers progress, they develop microenvironments that suppress tumor-targeting cytotoxic effector T cells. Direct nutritional competition of effector T cells against metabolically active and voracious cancer cells restrict the metabolic activities required for effector T cell proliferation and function. Tumors also enhance the recruitment and activity of immune suppressor cells (Treg cells, MDSCs and M2 type macrophages) that depend on different metabolic pathways for their functions. Recently, it has been shown that small molecules manipulating metabolic pathways of cancer cells, T cells or immune suppressor cells can enhance anti-cancer immunities and suppress tumor growth. For instance, metformin enhances development of memory T cell by switching cellular metabolism from glycolysis to mitochondrial respiration. Moreover, suppression of MDSCs by an inhibitor of fatty acid oxidation was also shown to inhibit tumor growth, raising an exciting possibility of reinvigorating anti-cancer immunity by small molecules targeting cellular metabolic pathways.
Tumor cells promote differentiation and recruitment of immunosuppressive cells to the tumor microenvironment, and these suppressive cells play a crucial role in evasion of cancer cells from the host’s immune surveillance. The inhibitors of immunosuppressive cells boost anti-cancer immunity and are expected to synergize with existing immunotherapies. We have identified a series of novel small molecules that target immunosuppressive cells and augment the anti-cancer immunity. Our compounds preferentially target the immunosuppressive cells in the tumor microenvironment. We are in the process of lead optimization and investigating the synergistic effects with the anti-PD-1 antibody in mice. We expect to complete the lead optimization in 2016 and initiate the first human studies in 2018.
Go to Pipeline
Copyright © ImmunoMet. All rights reserved.