Pioneering the next frontier in cancer immunotherapy
Despite the increasing use of immuno-oncology drugs and targeted therapies, complete and durable responses are observed in only a subset of patients; and most patients’ cancers advance even while receiving therapy. With the aim of improving current standard of care, we are developing our therapeutic candidates as monotherapies and in combination with approved drugs with the goal of curing cancer.
The more fundamental a role in immune suppression a metabolite plays, the more likely it is to be an effective therapeutic target across multiple tumor types, ultimately benefiting more patients. Therefore, our research focuses on immuno-metabolic pathways which have the potential to impact both the adaptive and innate immune system relevant in a broad range of tumor types.
Activation of metabolic pathways can lead to a number of local changes that promote tumor survival. These immune suppressive pathways have broad effects including decreased T cell expansion and tumor infiltration and increased immune suppressor cells such as myeloid-derived suppressor cells (MDSCs) and T regulatory cells.
What is an immunosuppressive metabolite?
Immunosuppressive metabolites are molecules that are formed by a breakdown of a ‘precursor’ that function to suppress an immune response. These metabolites inhibit the activity of effector immune cells such as cytotoxic T-cells or by increasing the activity of regulatory immune cells such as myeloid-derived suppressor cells. Multiple metabolic pathways are upregulated in cancer leading to increased concentrations of immunosuppressive metabolites enabling cancer cells to evade recognition of effector immune cells.
Common characteristics of an immunosuppressive tumor microenvironment
- Secretion of immunosuppressive molecules
- Generation of immunosuppressive metabolites
- Infiltration of regulatory immune cells
- Incidence of anergic effector T cells
- Expression of immune-activating molecules
- Penetration of proinflammatory helper and effector immune cells
- Tumor antigen presentation
Tackling the protective tumor micro-environment
Tumors cause a number of structural and chemical changes in the surrounding area, referred to as the “tumor micro-environment” or TME. These changes in the surrounding cells and tissues promote tumor survival. At Kyn Therapeutics, we are focused on reversing these changes to enhance immunity, and allow responding immune cells to reach the tumor.
Key publications in immunometabolism