Methods of activating and proliferating exhausted CD8 T cells, CD8 T cells with enhanced activity prepared by the same, and uses thereof

A pharmaceutical composition for treating cancer comprising CD8 T cells whose overexpression of Klf4 protein is induced as an effective ingredient, wherein the CD8T cells whose overexpression of Klf4 protein is induced are prepared by transfecting the CD8 T cell with (a) an expression vector containing a polynucleotide encoding the Klf4 protein or (b) an mRNA expressing the Klf4 protein.

A transduced CD8 T cell which is transformed to overexpress the Klf4 protein, wherein the transduced CD8 T cell is prepared by transfecting the CD8 T cell with (a) an expression vector containing a polynucleotide encoding the Klf4 protein or (b) an mRNA expressing the Klf4 protein.

A transduced CAR-CD8 T cell prepared by transducing a CD8 T cell isolated from a subject in need thereof or a cell population containing the CD8 T cell whose overexpression of Klf4 protein is induced with a gene encoding a chimeric antigen receptor (CAR), wherein the transduced CD8 T cell is prepared by transfecting the CD8 T cell with (a) an expression vector containing a polynucleotide encoding the Klf4 protein or (b) an mRNA expressing the Klf4 protein.

A composition comprising transformed CD8 T cells transduced to overexpress Klf4 protein, a cell population containing the transduced CD8 T cells, or a transduced CAR-CD8 T cells transduced to overexpress Klf4 protein and a chimeric antigen receptor (CAR).

A method of treating a subject suffering from cancer comprising:

• preparing CD8 T cell-cells selected from the group consisting of a) CD8 T cells isolated from the subject, b) a cell population comprising the CD8 T cells, and c) transduced CAR-CD8 T cells prepared by transducing the CD8 T cells with a gene encoding a CAR;
• inducing overexpression of Klf4 protein in the CD8 T cell-containing cells by transducing the CD8 T cell-containing cells with (a) an expression vector containing a polynucleotide encoding the Klf4 protein or (b) an mRNA expressing the Klf4 protein, or treating the CD8 T cell-containing cells with a Klf4 inducer;
• and administrating the CD8 T cell-containing cells whose expression of Klf4 protein is induced to the subject.

An in vitro method of enhancing immune response of CD8 T cells comprising inducing overexpression of Klf4 protein in the cells, wherein the cells are selected from the group consisting of a) CD8 T cells isolated from a subject, b) a cell population comprising the CD8 T cells, and c) CAR-CD8 T cells prepared by transducing the CD8 T cells with a gene encoding a chimeric antigen receptor (CAR).

An in vitro method of proliferating CD8 T cells isolated from a subject comprising inducing overexpression of Klf4 protein in CD8 T cell-containing cells selected from the group consisting of a) CD8 T cells isolated from a subject, b) a cell population comprising the CD8 T cells, and c) CAR-CD8 T cells prepared by transducing the CD8 T cells with a gene encoding a chimeric antigen receptor (CAR).

A pharmaceutical composition for treating cancer comprising CD8 T cell-containing cells whose expression of Klf4 is induced, wherein the cells are selected from the group consisting of:

• a) CD8 T cells isolated from a subject, b) a cell population containing the CD8 T cells, and c) CAR-CD8 T cells prepared by transducing the CD8 T cell-containing cells with a gene construct encoding a chimeric antigen receptor as an active ingredient, wherein the CD8 T cell-containing cells whose expression of Klf4 is induced are prepared by transfecting the CD8 T cells or the CAR-CD8 T cells with (a) an expression vector containing a polynucleotide encoding the Klf4 protein or (b) an mRNA expressing the Klf4 protein.