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AssigneeThe Scripps Research Institute
InventorsPeng Wu, Yujie Shi, Yingqin Hou
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Provided herein are methods for expanding activated T cells to produce T cells with less differentiated status and enhanced in vivo persistence after adoptive transfer. Activated T cells suitable for the methods include, e.g., progenitor exhausted (Tim3−TCF-1+), stem memory, and central memory T cells. The invention also provides methods for identifying progenitor exhausted T cells specific to an antigen. Further, the invention provides progenitor exhausted T cells, pharmaceutical compositions, and kits as well as methods for the treatment of cancer or infection using the same.
A method of expanding activated T cells to produce T cells with enhanced in vivo persistence after adoptive transfer, comprising contacting a cell population comprising activated T cells with an effective amount of a compound that uncouples T cell expansion from differentiation, thereby expanding the activated T cells to produce T cells with enhanced in vivo persistence after adoptive transfer.
A method for converting a TCF-1 negative T cell into partially TCF-1 positive, comprising contacting a population of TCF-1 negative T cells with an effective amount of a compound that uncouples T cell expansion from differentiation, thereby converting the TCF-1 negative T cell into partially TCF-1 positive.
A kit for in vitro expansion of an activated T cell for adoptive cell therapy, comprising (1) an effective amount of a compound that uncouples T cell expansion from differentiation, and (2) an instruction of co-culturing the compound with a population of cells comprising the activated T cell.
A method of screening for compounds that promote proliferation of activated T cells and/or maintain expanded T cells in a less differentiated state, comprising:
Dependencies are inferred from the claim text.