T CELL-ANTIGEN COUPLER WITH VARIOUS CONSTRUCT OPTIMIZATIONS
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Abstract
A trifunctional molecule is provided, comprising (i) a target-specific ligand, (ii) a ligand that binds a protein associated with a TCR complex, and (iii) a T cell receptor signaling domain polypeptide. Variants of the molecule are provided, including variants that exhibit optimized surface expression, transduction efficiency, and effector functionality. Variations include, for example, different ligands that bind CD3 epsilon (e.g., OKT3, L2K, F6A, UCHT1 and humanized UCHT1), different signaling domains, and different linkers between domains.
14 Citations
119 Claims
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1-99. -99. (canceled)
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100. A nucleic acid sequence encoding a CD19 Trifunctional T cell-antigen coupler (CD19-TAC) comprising:
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(a) a first polynucleotide encoding a ligand that selectively binds a CD19 antigen; (b) a second polynucleotide encoding a humanized variant of a UCHT1 (huUCHT1) ligand comprising a Y177T mutation (huUCHT1 (Y177T)) that binds CD3; and (c) a third polynucleotide encoding a polypeptide comprising a CD4 cytosolic domain and a CD4 transmembrane domain; wherein ligand encoded by (a), ligand encoded by (b), and polypeptide encoded by (c) are fused directly to each other, or joined by at least one linker. - View Dependent Claims (101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119)
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Specification