The application uses
gene editing technology to design and optimize a safe and controllable
chimeric antigen receptor loaded with a
suicide gene, and a macrophage expressing the same, the
chimeric antigen receptor comprising a single-chain variable region targeting
carcinoembryonic antigen (CEA), a
hinge region, a
transmembrane region, and an
intracellular signaling region. The application has the following advantages: the
chimeric antigen receptor-Hoxb8 macrophage CAR-Hoxb8-M has high infiltration, enhanced
phagocytosis and
antigen presentation capacity, and is expected to become a new strategy for the
immunotherapy of
solid tumor cells. The constructed stem
progenitor cells proliferate rapidly, can be obtained in large quantities in a short time, and can be frozen for long-term preservation. The induction of macrophages is short, simple and convenient, the macrophages efficiently express CAR, are stable and uniform,
small molecule compounds regulate the fate of
progenitor cells and macrophages, are safe and controllable, and have an anti-
colorectal cancer treatment effect. The CAR-Hoxb8-M combined with an
immune checkpoint inhibitor can further inhibit
tumor growth and improve
survival rate.