Modified immune cells having enhanced function and methods for screening the same
The present disclosure provides gene edited modified immune cells or precursors thereof (e.g., gene edited modified T cells) comprising an exogenous T cell receptor (TCR) and/or a chimeric antigen receptor (CAR) having specificity for a target antigen, and an insertion and/or deletion in one or more endogenous gene loci, wherein the endogenous gene loci encode regulators of T cell function, thereby resulting in immune cells having enhanced function. Compositions and methods of treatment are also provided. The present invention provides methods of screening for TCR- or CAR-T cells with enhanced immune function (e.g., T cell efficacy, T cell memory, and/or T cell persistence).
1. A modified immune cell or precursor cell thereof, comprising:
an insertion and/or deletion in one or more gene loci encoding for a protein selected from the group consisting of AZI2, C1orf141, CCDC33, CCL7, CEACAM19, MFSD5, PAGR1, SIX2, and USP27X, wherein the insertion and/or deletion is capable of downregulating gene expression of the one or more endogenous genes; and
an exogenous T cell receptor (TCR) and/or chimeric antigen receptor (CAR) comprising affinity for an antigen on a target cell.
2. The modified cell of claim 1 , wherein the antigen on a target cell is a tumor associated antigen (TAA).
3. The modified cell of claim 1 , wherein the modified immune cell is an autologous cell.
4. The modified cell of claim 1 , wherein the modified immune cell is derived from a human.
5. The modified cell of claim 1 , wherein the modified immune cell is a modified T cell.