Targeted replacement of endogenous t cell receptors
AssigneeThe Regents of the University of California
InventorsTheodore Lee Roth, Eric SHIFRUT, Alexander MARSON, Cristina PUIG SAUS, Antoni RIBAS
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Abstract
Provided herein are methods and compositions for editing the genome of a human T cell. In some embodiments, a heterologous T cell receptor (TCR)-β chain and a heterologous TCR-α chain are inserted into exon 1 of a TCR subunit constant gene in the genome of the T cell.
Claims21
1-30. (canceled)
A method of treating a subject having a cancer that expresses a target antigen, comprising:
- administering to the subject having the cancer a modified primary human T cell comprising:
- at least one nucleic acid sequence comprising at least one heterologous gene non-virally inserted into one or both of:
- an endogenous T cell receptor alpha subunit constant gene (TRAC);
- and
- an endogenous T cell receptor beta subunit constant gene (TRBC), wherein the at least one heterologous gene encodes at least one antigen-specific receptor that specifically binds the target antigen expressed by the cancer, and wherein the at least one nucleic acid sequence is at least 500 bp in size.
A method of editing the genome of a primary human T cell, comprising:
- a. obtaining the primary human T cell;
- b. editing the genome of the human T cell by non-virally inserting into one or both of:
- an endogenous T cell receptor alpha subunit constant gene (TRAC);
- and
- an endogenous T cell receptor beta subunit constant gene (TRBC),
- at least one nucleic acid sequence comprising at least one heterologous gene encoding at least one antigen-specific receptor that specifically binds a target antigen expressed by a cancer.
A primary human T cell comprising at least one nucleic acid sequence comprising at least one heterologous gene non-virally inserted into one or both of:
- an endogenous T cell receptor alpha subunit constant gene (TRAC);
- and
- an endogenous T cell receptor beta subunit constant gene (TRBC),
- of the primary human T cell, wherein the at least one heterologous gene encodes a receptor that specifically binds a target antigen expressed by a cancer.
Dependencies are inferred from the claim text.