Immunogenic cell death (ICD) is a regulated cell death that engages the adaptive arm of the immune system. It is characterized by the release soluble factors and mis-localisation of membrane-bound proteins to enhance so-called Damage Associated Molecular Patterns (DAMPs) that boost the function of immune cells.
We have screened our small molecule collection for molecules that induce ICD in three tumor cell lines (two human, MDA-MB-231 & U2-OS and one mouse, Hepa1-6). We have identified two novel chemical series potently activating DAMPs in all three tumor cell lines. Our priority chemical series potently (100nM EC50) induces human DC phagocytosis confirming that ENYO’s molecules stimulate the adaptive immune response to treated tumor cells. Additional evidence that ENYO’s molecules induce ICD comes from a preliminary in vivo study demonstrating that compound treatment results in a reduced rate of growth of an explanted MDA-MB-231 tumor and also results in enhanced immune cell recruitment into the tumor.
We predict that poorly immunogenic tumors will be more responsive to immunotherapy when combined with ICD inducers and that molecules with such actions will become an important part of clinical combination approaches to enable maximal immune response to malignant cells.