These studies advance work using human induced pluripotent stem cells (iPSCs) as a platform to produce genetically modified immune cells with improved anti-tumor activity. Specifically, this work demonstrates the ability to express novel chimeric antigen receptors (CARs) in iPSCs and subsequently differentiate those engineered cells to produce CAR-expressing macrophages (iPSC-CARMACs). These iPSC-CARMACs demonstrate improved anti-tumor activity in vitro and in vivo compared to non-CAR-expressing iPSC-derived macrophages. Additionally, iPSC-CARMACs combined with anti-CD47 antibody treatment further improves their anti-tumor activity. 

Macrophage-based therapy is gaining interest to generate improved anti-tumor activity, especially against solid tumors that are typically resistant to CAR-expressing T cells. CAR-expressing macrophages derived from peripheral blood macrophages of patients are already in clinical trials. We anticipate that iPSC-CARMACs will provide a more standardized source of engineered macrophage-based therapy and we are moving toward clinical translation of this work.