The present invention provides a
chimeric antigen receptor based on the
intracellular domain, comprising sequentially linked
extracellular domains, transmembrane domains, and
intracellular domains, wherein the
extracellular domain comprises an
antigen recognition region and a
hinge region, and the
intracellular domain comprises sequentially linked CD3ε
intracellular domain cleavage, a co-stimulatory signaling region, and a CD3ζ
intracellular domain. Compared to prior art, the provided
chimeric antigen receptor exhibits superior therapeutic effects and fewer side effects, as reflected in improved
membrane surface CAR molecule levels of CAR-T cells, better immune
synapse formation, superior
antigen sensitivity, fewer cytokines, better growth capacity, better sustained proliferation capacity, better repeated killing capacity, reduced NK
cell activation and
cell depletion, and an increase in
stem cell-like and
memory cell subsets of CAR-T cells. Furthermore, the
chimeric antigen receptor can further enhance the
therapeutic effect on tumors and, at the same time, reduce the production of inflammatory cytokines associated with the activation of macrophages and monocytes by downregulating its own cytokines, thereby enabling early prevention of
cytokine storms.