Galunisertib

Galunisertib is a TGF-B kinase (ALK5) antagonist.1 It stimulated hematopoiesis from primary myelodysplastic syndrome bone marrow specimens via downregulation of SMAD2 phosphorylation.2 It has been in clinical trials for treatment of various cancers.3-5 Galunisertib has more recently been used to enhance the anti-neuroblastoma activity of anti-GD2 antibody Dinutuximab with natural killer cells6 and preserved the function of in vitro expanded natural killer cells in AML and colon cancer models7. Galunisertib reversed TGF and regulatory T cell mediated suppression of human T cell proliferation. In combination with PD-L1 blockade, it resulted in improved tumor growth inhibition and complete regressions in colon carcinoma models.8