Genetically-modified cells comprising a modified human T cell receptor alpha constant region gene
AssigneePrecision BioSciences, Inc.
InventorsDerek Jantz, James Jefferson Smith, Michael G. Nicholson, Daniel T. MacLeod, Victor Bartsevich, Jeyaraj Antony
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Abstract
Disclosed herein is a genetically-modified cell comprising in its genome a modified human T cell receptor alpha constant region gene, wherein the cell has reduced cell-surface expression of the endogenous T cell receptor. The present disclosure further relates to methods for producing such a genetically-modified cell, and to methods of using such a cell for treating a disease in a subject.
Claims9
A population of genetically-modified human T cells, wherein between 20% and 65% of cells in said population express a cell-surface chimeric antigen receptor and exhibit reduced cell-surface expression of the endogenous T cell receptor (TCR) when compared to unmodified control cells, wherein said cells expressing said chimeric antigen receptor comprise in their genome a modified human TCR alpha constant region gene, wherein said modified human TCR alpha constant region gene comprises from 5′ to 3′:
- (a) a 5′ region of a human TCR alpha constant region gene which is endogenous to said T cell;
- (b) an exogenous nucleic acid sequence encoding said chimeric antigen receptor;
- and
- (c) a 3′ region of said human TCR alpha constant region gene which is endogenous to said T cell;
- wherein said chimeric antigen receptor comprises a ligand-binding domain having specificity for an antigen present on a cancer cell.
Dependencies are inferred from the claim text.