563TiP A phase I, first in human (FIH) study of adenovirally transduced autologous macrophages engineered to contain an anti-HER2 chimeric antigen receptor (CAR) in subjects with HER2 overexpressing solid tumors

Abstract

T cell therapies have led to remarkable advances in hematologic malignancies, but not in solid tumors (ST). Macrophages are actively recruited into, and abundantly present in the solid tumor microenvironment (sTME). Tumor associated macrophages are typically immunosuppressive, but can be engineered with a CAR to be proinflammatory, recognize and phagocytose antigen overexpressing cancer cells, reprogram the sTME and present neoantigens to T cells, leading to epitope spreading and immune memory. HER2 is overexpressed in many cancers, including but not limited to breast and gastroesophageal (table).