CAR-Macrophages and CAR-T Cells Synergistically Kill Tumor Cells In Vitro

Liu，Maoxuan1; Liu，Junchen1,2; Liang，Ziwei3; Dai，Kun1; Gan，Jiangyu1; Wang，Qi1,2; Xu，Yang3; Chen，Youhai H.1,2; Wan，Xiaochun1,2

2022-11-01

10.3390/cells11223692

Cells   Impact Factor & Quartile

2073-4409

Chimeric antigen receptor (CAR)-expressing macrophages (CAR-M) have a great potential to improve cancer therapy, as shown from several recent preclinical studies. However, unlike CAR-T cell therapy, which has been widely studied, the efficacy and limitations of CAR-M cells remain to be established. To address this issue, in the present study, we compared three intracellular signaling domains (derived from common γ subunit of Fc receptors (FcRγ), multiple EGF-like-domains protein 10 (Megf10), and the CD19 cytoplasmic domain that recruits the p85 subunit of phosphoinositide-3 kinase (PI3K), respectively) for their ability to promote primary CAR-M functions, and investigated the potential synergistic effect between CAR-M and CAR-T cells in their ability to kill tumor cells. We found that CAR-M exerted more potent phagocytic and tumor-killing capacity than CAR-M and CAR-M. CAR-M and CAR-T demonstrated synergistic cytotoxicity against tumor cells in vitro. Mechanistically, the inflammatory factors secreted by CAR-T increased the expression of costimulatory ligands (CD86 and CD80) on CAR-M and augmented the cytotoxicity of CAR-M by inducing macrophage M1 polarization. The upregulated costimulatory ligands may promote the fitness and activation of CAR-T cells in turn, achieving significantly enhanced cytotoxicity. Taken together, our study demonstrated for the first time that CAR-M could synergize with CAR-T cells to kill tumor cells, which provides proof-of-concept for a novel combinational immunotherapy.

CAR-M CAR-T FcRγ immunotherapy synergy

SCI

English

Others

Special Funds for Major Science and Technology of Guangdong Province[2019B020201014] ; National Key R&D Program of China[2019YFA0906100] ; Guangdong Basic and Applied Basic Research Foundation[2021A1515110054] ; Science and Technology Innovation Fund of Shenzhen["JCYJ20170818164619194","JCYJ20210324101400001"]

Cell Biology

Cell Biology

WOS:000887075300001

MDPI

2-s2.0-85142541704

Scopus

1.Guangdong Immune Cell Therapy Engineering and Technology Research Center,Center for Protein and Cell-Based Drugs,Institute of Biomedicine and Biotechnology,Shenzhen Institute of Advanced Technology,Chinese Academy of Sciences,Shenzhen,518055,China
2.College of life Sciences,University of Chinese Academy of Sciences,Beijing,100049,China
3.School of Medicine,Southern University of Science and Technology,Shenzhen,518055,China

Liu，Maoxuan,Liu，Junchen,Liang，Ziwei,et al. CAR-Macrophages and CAR-T Cells Synergistically Kill Tumor Cells In Vitro[J]. Cells,2022,11(22).

Liu，Maoxuan.,Liu，Junchen.,Liang，Ziwei.,Dai，Kun.,Gan，Jiangyu.,...&Wan，Xiaochun.(2022).CAR-Macrophages and CAR-T Cells Synergistically Kill Tumor Cells In Vitro.Cells,11(22).

Liu，Maoxuan,et al."CAR-Macrophages and CAR-T Cells Synergistically Kill Tumor Cells In Vitro".Cells 11.22(2022).