Hillstream BioPharma, Inc., a biotechnology company developing novel therapeutic candidates targeting ferroptosis, an emerging new anti-cancer mechanism resulting in iron mediated cell death for drug resistant and devastating cancers, today announced a collaboration with Sapien Biosciences to evaluate the synergy of HSB-1216 with immune checkpoint inhibitors. Immune Checkpoint Inhibitors and Ferroptosis Treatment with immune checkpoint inhibitors (ICIs) induces the effector function of T cells in the tumor microenvironment (TME). Activated T cells accumulated in TME then kill tumor cells mainly by enhancing cell death through the granzyme pathway and by releasing interferon gamma (IFN?) from CD8 + T cells. Ferroptosis is a newly defined form of cell death, that is different than apoptosis, necrosis or autophagy, and results from iron-dependent accumulation of lipid reactive oxygen species or lipid peroxidation. Recent studies published [Nature, 569 (7755):270-274, 2019] describe that immunotherapy-activated CD8 + T cells enhance ferroptosis-specific lipid peroxidation in tumor cells leading to the anti-tumor effect of immunotherapy. Activated CD8 + T cells by treatment with ICIs promote tumor cell lipid peroxidation and thereby sensitize tumor cells to ferroptosis inducers through IFN?. The study concluded that inducing the Ferroptotic pathway in combination with checkpoint blockade is a potential synergistic therapeutic approach.
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