Humanized gucy2c t cell-antigen couplers and uses thereof
AssigneeTriumvira Immunologics USA, Inc.
InventorsAndreas Bader, Christopher W. Helsen, Philbert Ip, Stacey X. Xu, Tania Benatar, Thanyashanthi Nitya-Nootan
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Abstract
GUCY2C T cell antigen coupler (TAC) polypeptides having (i) an antigen-binding domain that binds GUCY2C (e.g., a nanobody), (ii) an antigen-binding domain that binds a protein associated with a TCR complex, and (iii) a T cell receptor signaling domain polypeptide are provided.
Claims47
A Guanylate Cyclase 2C (GUCY2C) T cell-antigen coupler (GUCY2C-TAC) protein, comprising:
- (a) a first polypeptide comprising a GUCY2C-binding domain comprising:
- (i) a CDR1 having the amino acid sequence of SEQ ID NO:
- 72, a CDR2 having the amino acid sequence of SEQ ID NO:
- 73, and a CDR3 having the amino acid sequence of SEQ ID NO:
- 74;
- or
- (ii) a CDR1 having the amino acid sequence of SEQ ID NO:
- 75, a CDR2 having the amino acid sequence of SEQ ID NO:
- 76, and a CDR3 having the amino acid sequence of SEQ ID NO:
- 77;
- (b) a second polypeptide comprising an antigen-binding domain that binds a protein associated with a TCR complex;
- and
- (c) a third polypeptide comprising a TCR co-receptor cytosolic domain and transmembrane domain;
- wherein, the first polypeptide, the second polypeptide, and the third polypeptide are fused directly to each other, or joined by at least one linker.
A GUCY2C TAC protein comprising an amino acid sequence having at least 80% sequence identity with the amino acid sequence of any one of SEQ ID NOs:
- 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101, 103, 105, 107, 109, 111, 113, 115, 117, 119, 121, 123, 125, 127, 129, 131, 133, 135, 137, 139, 141, 143, 145, 147, 149, 151, and 153.
A GUCY2C TAC protein comprising an amino acid sequence according to the amino acid sequence of any one of SEQ ID NOs:
- 79, 81, 83, 85, 87, 89, 91, 93, 95, 97, 99, 101, 103, 105, 107, 109, 111, 113, 115, 117, 119, 121, 123, 125, 127, 129, 131, 133, 135, 137, 139, 141, 143, 145, 147, 149, 151, and 153.
A GUCY2C TAC protein comprising an amino acid sequence having at least 80% sequence identity with the amino acid sequence of SEQ ID NO:
- 131, A GUCY2C TAC protein comprising an amino acid sequence according to the amino acid sequence of SEQ ID NO:
- 131.
Dependencies are inferred from the claim text.