Mutated t cell receptor beta chain
AssigneeThe Regents of the University of California
InventorsJustin Eyquem, Christopher Chang
Life of this patent
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Abstract
The disclosure provides compositions and methods for generating a population of engineered immune cells, e.g., T cells, that express recombinant or synthetic T cell receptors and are depleted of cells that express endogenous T cell receptors. The disclosure further provides therapeutic methods employing such populations.
Claims40
A nucleic acid encoding a human T Cell Receptor (TCR) beta chain comprising a mutated constant region having at least 95% sequence identity to any one of SEQ ID NOS:1, 2, or 3, wherein the constant region comprises a substitution at a position corresponding to position D111, wherein the substitution is any amino acid other than E or G.
A nucleic acid encoding a human TCR beta chain polypeptide comprising a mutated constant region having at least 95% sequence identity to any one of SEQ ID NOS:1, 2, or 3, wherein the constant region comprises at least one substitution at a position corresponding to position G101.
A nucleic acid encoding a human TCR beta chain polypeptide comprising a mutated constant region having at least 95% sequence identity to any one of SEQ ID NOS:1, 2, or 3, wherein the constant region comprises at least one substitution at a position corresponding to position G115.
A nucleic acid encoding a human TCR beta chain polypeptide comprising a mutated constant region having at least 95% sequence identity to any one of SEQ ID NOS:1, 2, or 3, wherein the constant region comprises at least one substitution at a position corresponding to position W108, Q118, C130, or G131, wherein the substitution at position 108 is A, R, M or L;
- the substitution at position 130 is V, E, L or I;
- or the substitution at position 131 is N, wherein the substitution reduces binding of an antibody BW242/412 to the mutated constant region.
A host cell comprising the nucleic acid of any one of the foregoing claims.
The host cell of claim 30, wherein the host cell is edited to disrupt expression of endogenous TCR-alpha chain.
A library of cells that express mutated TCR beta constant regions wherein the library comprises cells comprising different mutations of the TCR beta constant region that span the constant region domain.
Dependencies are inferred from the claim text.