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AssigneeMcMaster University
InventorsChristopher W. HELSEN, Jonathan BRAMSON, Anna DVORKIN-GHEVA, Galina F. DENISOVA, Ksenia BEZVERBNAYA, Kenneth Anthony MWAWASI
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A trifunctional molecule comprising a target-specific ligand, a ligand that binds a protein associated with the TCR complex and a T cell receptor signaling domain polypeptide is provided. The ligand that binds a protein associated with a TCR complex is UCHT1 with a Y182T mutation. Engineering T cells with this novel receptor engenders antigen specific activation of numerous T cell functions, including cytokine production, degranulation and cytolysis.
A nucleic acid sequence encoding a Trifunctional T cell-antigen coupler (Tri-TAC) comprising:
A nucleic acid sequence encoding a T cell-antigen coupler (Tri-TAC) comprising:
A nucleic acid sequence encoding a T cell-antigen coupler (Tri-TAC) comprising:
The nucleic acid sequence of any one of claims 1-13, wherein the protein associated with a TCR complex is CD3, preferably CD3ε.
A nucleic acid sequence encoding an anti-HER-2 Trifunctional T cell-antigen coupler (anti-HER-2 Tri-TAC) comprising:
A nucleic acid sequence encoding an anti-BCMA Trifunctional T cell-antigen coupler (anti-BCMA Tri-TAC) comprising:
The nucleic acid sequence of claim 56, wherein the peptide linker comprises a G4S3 linker.
A method of treating a cancer expressing a target antigen in an individual in need thereof, comprising administering to the individual an engineered T cell comprising a nucleic acid sequence encoding a Trifunctional T cell-antigen coupler (Tri-TAC) comprising:
A method of treating a cancer expressing a target antigen in an individual in need thereof, comprising administering to the individual an engineered T cell comprising a nucleic acid sequence encoding a Trifunctional T cell-antigen coupler (Tri-TAC) comprising:
A method of treating a cancer expressing a target antigen in an individual in need thereof, comprising administering to the individual an engineered T cell comprising a nucleic acid sequence encoding a T cell-antigen coupler (Tri-TAC) comprising:
A method of treating a cancer expressing a HER-2 antigen in an individual in need thereof, comprising administering to the individual an engineered T cell comprising a nucleic acid sequence encoding an anti-HER-2 Trifunctional T cell-antigen coupler (anti-HER-2 Tri-TAC) comprising:
A method of treating a cancer expressing a BCMA antigen in an individual in need thereof, comprising administering to the individual an engineered T cell comprising a nucleic acid sequence encoding an anti-BCMA Trifunctional T cell-antigen coupler (anti-BCMA Tri-TAC) comprising:
Dependencies are inferred from the claim text.