Immune cells with enhanced cytotoxicity and methods of use thereof
AssigneesLudwig Institute for Cancer Research, The Wistar Institute
InventorsZandra Walton, Zachary Stine, Yaoyu Gong, Chi V. Dang
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Abstract
This disclosure provides methods for enhancing antitumor cytotoxicity of immune cells by introducing to the immune cells a genetic modification that comprises overexpression of RHEB or a functional fragment thereof, overexpression of LAMP 1-RHEB or a functional fragment thereof, overexpression of CA9 or a functional fragment thereof, overexpression of NHE1 or a functional fragment thereof, or combination thereof.
Claims20
A method for enhancing antitumor cytotoxicity of immune cells, comprising introducing to the immune cells a genetic modification that comprises overexpression of NHE1 or a functional fragment thereof, wherein overexpression of NHE1 or a functional fragment thereof enhances antitumor cytotoxicity of the modified immune cells against tumor cells in an acidic tumor microenvironment, wherein the immune cells are cytotoxic natural killer cells, and wherein the NHE1 is a constitutively active NHE1 comprising an amino acid sequence of SEQ ID NO:
- 6.
A modified immune cell comprising a genetic modification that comprises overexpression of NHE1 or a functional fragment thereof, wherein the modified immune cell is a cytotoxic natural killer cell, wherein overexpression of NHE1 or a functional fragment thereof enhances antitumor cytotoxicity of the modified immune cell against tumor cells in an acidic tumor microenvironment, and wherein the NHE1 is a constitutively active NHE1 comprising an amino acid sequence of SEQ ID NO:
- 6.
Dependencies are inferred from the claim text.