Authors
Michael Klichinsky, Marco Ruella, Olga Shestova, Xueqing Maggie Lu, Andrew Best, Martha Zeeman, Maggie Schmierer, Konrad Gabrusiewicz, Nicholas R Anderson, Nicholas E Petty, Katherine D Cummins, Feng Shen, Xinhe Shan, Kimberly Veliz, Kristin Blouch, Yumi Yashiro-Ohtani, Saad S Kenderian, Miriam Y Kim, Roddy S O’Connor, Stephen R Wallace, Miroslaw S Kozlowski, Dylan M Marchione, Maksim Shestov, Benjamin A Garcia, Carl H June, Saar Gill
Publication date
2020/8
Journal
Nature biotechnology
Volume
38
Issue
8
Pages
947-953
Publisher
Nature Publishing Group US
Description
Chimeric antigen receptor (CAR) T cell therapy has shown promise in hematologic malignancies, but its application to solid tumors has been challenging, , –. Given the unique effector functions of macrophages and their capacity to penetrate tumors, we genetically engineered human macrophages with CARs to direct their phagocytic activity against tumors. We found that a chimeric adenoviral vector overcame the inherent resistance of primary human macrophages to genetic manipulation and imparted a sustained pro-inflammatory (M1) phenotype. CAR macrophages (CAR-Ms) demonstrated antigen-specific phagocytosis and tumor clearance in vitro. In two solid tumor xenograft mouse models, a single infusion of human CAR-Ms decreased tumor burden and prolonged overall survival. Characterization of CAR-M activity showed that CAR-Ms expressed pro-inflammatory cytokines and chemokines, converted …
Scholar articles
M Klichinsky, M Ruella, O Shestova, XM Lu, A Best… - Nature biotechnology, 2020