Cytokine receptor genes and the use thereof to enhance therapy
Cells, such a T-cells, are provided that comprise cytokine receptors having increased activity in response to their ligand. For example, cell can comprise IL-2 and/or IL-15 receptors having increased surface expression or signaling activity. Cells of the embodiments have a significant growth advantage in the presence of cytokines and can be used, e.g., for enhanced adoptive cell transfer therapies.
1. An isolated T-cell comprising a recombinant vector comprising a nucleic acid molecule encoding the IL-2α receptor.
2. The isolated transgenic T-cell of claim 1 , wherein the isolated transgenic T-cell is a human T-cell.
3. The isolated transgenic T-cell of claim 1 , wherein the T-cell is a T-cell targeted to a cancer cell antigen.
4. The isolated transgenic T-cell of claim 3 , wherein the cancer cell antigen is GP240, 5T4, HER1, CD-33, CD-38, VEGFR-1, VEGFR-2, CEA, FGFR3, IGFBP2, IGF-1R, BAFF-R, TACI, APRIL, Fn14, EGFR, ERBB2, ERBB3 CD19, CD20 or mesothelin.
5. The isolated transgenic T-cell of claim 1 , wherein the T-cell expresses a chimeric antigen receptor (CAR) or a recombinant T-cell receptor (TCR).
6. The isolated transgenic T-cell of claim 1 , wherein the mutation increases surface expression, increases stability or increases ligand binding of the IL-2α receptor polypeptide.
7. The isolated transgenic T-cell of claim 1 , comprising the nucleic acid molecule encoding the IL-2α receptor is operably linked to a heterologous promoter.
8. The isolated transgenic T-cell of claim 7 , wherein the heterologous promoter is a ligand inducible promoter.
9. The isolated transgenic T-cell of claim 1 , wherein the nucleic acid molecule encoding IL-2Rα comprises a mutation that increases the activity of the IL-2Rα.