Insertable variable fragments of antibodies and modified α1-α2 domains of NKG2D ligands, and non-natural NKG2D ligands that bind non-natural NKG2D receptors
AssigneeXyphos Biosciences Inc.
InventorsKyle Landgraf, Daniel P. Steiger, Tarah Baron, Dana Gebhart
Life of this patent
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Abstract
This application relates generally to the production of polypeptides having specific antigen-binding properties of Fv domains, for example, insertable variable fragments of antibodies, and modified α1-α2 domains of NKG2D ligands.
Claims23
A non-natural NKG2D receptor, wherein said non-natural NKG2D receptor is a chimeric NKG2D receptor that comprises an ectodomain comprising the amino acid sequence of SEQ ID NO:
- 75 but in which the tyrosine at position 73 of SEQ ID NO:
- 75 has been replaced with alanine.
A chimeric antigen receptor comprising a non-natural NKG2D receptor ectodomain comprising the amino acid sequence of SEQ ID NO:
- 75 but in which the tyrosine at position 73 of SEQ ID NO:
- 75 has been replaced with alanine.
A non-natural, modified α1-α2 domain of a NKG2D ligand that (a) binds a non-natural NKG2D receptor ectodomain comprising the amino acid sequence of SEQ ID NO:
- 75 but in which the tyrosine at position 73 of SEQ ID NO:
- 75 has been replaced with alanine, and that (b) comprises the amino sequence of SEQ ID NO:
- 57 but in which one or more of the amino acids at positions 71, 72, 73, 74, 75, 155, 156, 157, 158, and 159 have been replaced, the amino acid sequence of SEQ ID NO:
- 87 but in which one or more of the amino acids at positions 154, 155, 156, 157, 158, and 159 have been replaced, or the amino acid sequence of SEQ ID NO:
- 89 but in which one or more of the amino acids at positions 155, 156, 157, 158, and 159 have been replaced.
A non-natural, modified α1-α2 domain that comprises SEQ ID NO:
- 90, 91, 92, 93, 94, 95, or 96.
A method of killing a cell comprising contacting the cell with a fusion protein comprising a non-natural, modified α1-α2 domain that comprises SEQ ID NO:
- 90, 91, 92, 93, 94, 95, or 96 fused to an antibody or antigen-binding antibody fragment, wherein the antibody or antigen-binding antibody fragment binds a target antigen on the cell, and also contacting the cell with a lymphocyte or NK cell comprising a chimeric antigen receptor comprising a non-natural NKG2D receptor ectodomain comprising the amino acid sequence of SEQ ID NO:
- 75 but in which the tyrosine at position 73 of SEQ ID NO:
- 75 has been replaced with alanine, to thereby kill the cell.
Dependencies are inferred from the claim text.