Tackling anti-tumor macrophage function through genome engineering

In the realm of cellular immunotherapies, the synthetic chimeric antigen receptor (CAR) has proven to be a revolutionary modality, leading to the US Food and Drug Administration approval of multiple autologous CAR T cell products. Despite their remarkable success in hematological malignancies, CAR T cell therapies have shown limited efficacy in solid tumors, prompting worldwide efforts to extend CAR engineering to alternative immune effector cells, including macrophages. Macrophages possess inherent qualities that are beneficial for immunotherapy, including tumor homing, clearance of malignant cells through phagocytosis, and initiation of an adaptive immune response through cytokine/chemokine signaling and antigen presentation.