Data from: Chimeric antigen receptors that trigger phagocytosis

Chimeric antigen receptors (CARs) are synthetic receptors that reprogram T
cells to kill cancer. The success of CAR-T cell therapies highlights the
promise of programmed immunity and suggests that applying CAR strategies
to other immune cell lineages may be beneficial. Here, we engineered a
family of Chimeric Antigen Receptors for Phagocytosis (CAR-Ps) that direct
macrophages to engulf specific targets, including cancer cells. CAR-Ps
consist of an extracellular antibody fragment, which can be modified to
direct CAR-P activity towards specific antigens. By screening a panel of
engulfment receptor intracellular domains, we found that the cytosolic
domains from Megf10 and FcRɣ robustly triggered engulfment independently
of their native extracellular domain. We show that CAR-Ps drive specific
engulfment of antigen-coated synthetic particles and whole human cancer
cells. Addition of a tandem PI3K recruitment domain increased cancer cell
engulfment. Finally, we show that CAR-P expressing murine macrophages
reduce cancer cell number in co-culture by over 40%.