RT Journal Article
SR Electronic
T1 Chimeric antigen receptors that trigger phagocytosis
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 316323
DO 10.1101/316323
A1 Meghan A. Morrissey
A1 Adam P. Williamson
A1 Adriana M. Steinbach
A1 Edward W. Roberts
A1 Nadja Kern
A1 Mark B. Headley
A1 Ronald D. Vale
YR 2018
UL http://biorxiv.org/content/early/2018/05/16/316323.abstract
AB 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 FcRγ robustly triggered engulfment independently of their native extracellular domain. We show that CAR-Ps drive specific engulfment of antigen-coated synthetic particles and whole cancer cells. Addition of a tandem PI3K recruitment domain increased cancer cell engulfment. Finally, we show that CAR-P expressing macrophages reduce cancer cell number in co-culture by over 40%.Summary We report the first Chimeric Antigen Receptors for Phagocytosis (CAR-Ps) that promote engulfment of antigen-coated particles and cancer cells.