Targeting a macrophage immune checkpoint

We have previously demonstrated that acute myeloid leukemia (AML) stem cells evade innate immune attacks by macrophages through CD47-SIRPα interactions (Theocharides et al., J. Exp. Med 2012). We could show that targeting this interaction with a fusion protein leads to the elimination of AML stem cells by phagocytosis. This fusion protein is now further evaluated in clinical trials for AML and other cancers. Our laboratory further evaluates the potential of compounds that synergistically act with anti-CD47 treatment. The goal of our investigations is to provide the rationale for the establishment of early phase clinical trials.