Chimeric antigen receptor
View Patent ↗Provided are a chimeric antigen receptor comprising an extracellular domain capable of binding to an antigen, a transmembrane domain and at least one intracellular domain, the chimeric antigen receptor being characterized in that an intracellular domain of a glucocorticoid-induced tumor necrosis factor receptor (GITR) is contained as the intracellular domain; a nucleic acid encoding the chimeric antigen receptor; a cell expressing the chimeric antigen receptor; and a method for producing the cell.
1. A nucleic acid encoding a chimeric antigen receptor comprising an extracellular domain capable of binding to an antigen, a transmembrane domain, and at least one intracellular domain, wherein the intracellular domain includes an intracellular domain of a glucocorticoid-induced tumor necrosis factor receptor (GITR), the intracellular domain further includes a CD3ζ intracellular domain, and the intracellular domain of GITR is arranged on a C-terminal side relative to the CD3ζ intracellular domain,
wherein a T cell or cell population comprising a T cell expressing the chimeric antigen receptor has an increased cytotoxic activity against a cell having the target antigen on the surface, as compared to a T cell or cell population comprising a T cell expressing a chimeric antigen receptor whose intracellular domain consists of an intracellular domain of CD28 and an intracellular domain of CD3ζ.
2. The nucleic acid encoding a chimeric antigen receptor according to claim 1 , wherein the antigen is a tumor antigen.
3. The nucleic acid encoding a chimeric antigen receptor according to claim 1 , wherein the extracellular domain capable of binding to an antigen is a single chain variable fragment of an antibody that binds to the antigen.
4. A chimeric antigen receptor comprising an extracellular domain capable of binding to an antigen, a transmembrane domain, and at least one intracellular domain, wherein the intracellular domain includes an intracellular domain of a GITR, the intracellular domain further includes a CD3ζ intracellular domain, and the intracellular domain of GITR is arranged on a C end side relative to the CD3ζ intracellular domain,
wherein a T cell or cell population comprising a T cell expressing the chimeric antigen receptor has an increased cytotoxic activity against a cell having the target antigen on the surface, as compared to a T cell or cell population comprising a T cell expressing a chimeric antigen receptor whose intracellular domain consists of an intracellular domain of CD28 and an intracellular domain of CD3ζ.
5. The chimeric antigen receptor according to claim 4 , wherein the antigen is a tumor antigen.
6. The chimeric antigen receptor according to claim 4 , wherein the extracellular domain capable of binding to an antigen is a single chain variable fragment of an antibody binding to the antigen.
7. A process for producing a chimeric antigen receptor-expressing cell, the process comprising a step of introducing the nucleic acid according to claim 1 into a cell, wherein the cell is a T cell or a cell population containing a T cell.
8. A chimeric antigen receptor-expressing cell in which the nucleic acid according to claim 1 is introduced, wherein the cell is a T cell or a cell population containing a T cell, and wherein the chimeric antigen receptor-expressing cell has an increased cytotoxic activity against a cell having the target antigen on the surface as compared to a cell expressing a chimeric antigen receptor whose intracellular domain consists of an intracellular domain of CD28 and an intracellular domain CD3ζ.