Gene knock-outs to improve t cell function
AssigneeSt. Jude Children's Research Hospital
InventorsHongbo CHI, Jun WEI, Terrence GEIGER, Wenting ZHENG
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Abstract
The present application provides methods of enhancing T cell function (e.g., expansion, persistence and/or effector functions), particularly by genetic modification of the Regnase-1, Batf, and additional genes (alone or in combination). The application also provides modified T cells manufactured using the methods provided by this invention and related pharmaceutical compositions. The application further provides methods of using the modified T cells for treating a disease (e.g., a cancer or an infectious disease).
Claims36
A method of enhancing expansion and/or persistence and/or an anti-tumor function and/or an anti-infection function of a T cell, comprising modifying one or more genes selected from Regnase-1 (REGNASE-1, Zc3h12a, MCPIP1), Ptpn2, Socs1, Agps, Rc3h1, and Rcor1 or gene product(s) thereof in the T cell such that the expression and/or function of said gene(s) or gene product(s) in the T cell is reduced or eliminated.
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A method of enhancing expansion and/or persistence and/or an anti-tumor function and/or an anti-infection function of a T cell, comprising increasing the expression of Batf gene and/or enhancing the function of BATF protein in the T cell.
46-47. (canceled)
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A method of improving mitochondrial biogenesis and/or function in a T cell comprising modifying one of more genes selected from Regnase-1 (REGNASE-1, Zc3h12a, MCPIP1), Ptpn2, Socs1, Agps, Rc3h1, and Rcor1 or gene product(s) thereof in the T cell such that the expression and/or function of said gene(s) or gene product(s) in the T cell is reduced or eliminated and/or increasing the expression of Batf gene and/or enhancing the function of BATF protein in the T cell.
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An isolated polynucleotide, comprising the nucleotide sequence of any one of SEQ ID NOs:
- 1-9, 29-34 and 36-42, or a nucleotide sequence having at least 80% identity thereof.
98-140. (canceled)
Dependencies are inferred from the claim text.