Method for enhancing a function of a T cell
Disclosed is a method for enhancing the function of a T cell, which is characterized by inhibiting the expression of programmed death-1 ligand 1 (PD-L1) and/or programmed death-1 ligand 2 (PD-L2) in the T cell. Also disclosed is a function-enhanced T cell which is produced by the function enhancement method. Further disclosed is a therapeutic agent comprising the function-enhanced T cell. The T cell can enhance an immune response to cancer, and is useful in an immunotherapy effective for cancer and the treatment or prevention of infectious diseases and autoimmune diseases.
1. A method for enhancing the function of a T cell, comprising:
suppressing ex vivo the expression of Programmed Death-1 Ligand 1 (PD-L1) and/or Programmed Death-1 Ligand 2 (PD-L2) of the T cell, wherein the expression of PD-L1 and/or PD-L2 is suppressed by siRNA for PD-L1 and/or PD-L2 which is directly introduced into the T cell or which is transcribed in the T cell, and
stimulating ex vivo the T cell,
wherein the function enhancement is the production enhancement of T cell interferon-γ (IFN-γ) and the production amount of IFN-γ in the T cell is increased as compared with a stimulated control T cell which is not suppressed by the siRNA.
2. The method for enhancing the function of a T cell according to claim 1 , wherein the T cell is a cytotoxic T cell or a regulatory T cell.
3. The method for enhancing the function of a T cell according to claim 2 , wherein the regulatory T cell is a helper T cell, a controlling T cell or a Th17 cell.
4. An isolated T cell with enhanced function, which is suppressed in the expression of PD-L1 and/or PD-L2 and stimulated, wherein the expression of PD-L1 and/or PD-L2 is suppressed by siRNA for PD-L1 and/or PD-L2 which is directly introduced into the T cell or which is transcribed in the T cell, and wherein the function enhancement is the production enhancement of T cell interferon-γ (IFN-γ) and the production amount of IFN-γ in the T cell is increased as compared with a stimulated control T cell which is not suppressed by the siRNA.
5. The isolated T cell with enhanced function according to claim 4 , wherein the T cell is a cytotoxic T cell or a regulatory T cell.
6. The isolated T cell with enhanced function according to claim 5 , wherein the regulatory T cell is a helper T cell, a controlling T cell or a Th17 cell.
7. A therapeutic agent for a disease showing sensitivity to the T cell with enhanced function according to claim 4 , comprising the T cell as an active ingredient.
8. A therapeutic agent for a disease showing sensitivity to the T cell with enhanced function according to claim 5 , comprising the T cell as an active ingredient.
9. A therapeutic agent for a disease showing sensitivity to the T cell with enhanced function according to claim 6 , comprising the T cell as an active ingredient.
10. The isolated T cell with enhanced function according to claim 4 , wherein the siRNA for PD-L1 comprises the nucleotide sequence of SEQ ID NO:1 or SEQ ID NO:9, and wherein the siRNA for PD-L2 comprises the nucleotide sequence of SEQ ID NO:2 or SEQ ID NO:11.
11. A T cell with enhanced function, which is suppressed in the expression of PD-L1 and/or PD-L2, wherein the expression of PD-L1 and/or PD-L2 is suppressed by siRNA for PD-L1 and/or PD-L2, wherein the siRNA for PD-L1 comprises the nucleotide sequence of SEQ ID NO:1 or SEQ ID NO:9, and wherein the siRNA for PD-L2 comprises the nucleotide sequence of SEQ ID NO:2 or SEQ ID NO:11.