Chimeric protein
AssigneeAutolus Limited
InventorsMartin Pulé, Brian Philip
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Abstract
The present invention provides a chimeric protein which comprises a multi-spanning transmembrane protein fused to a FAS endodomain, wherein the multi-spanning transmembrane protein binds an extracellular ligand, leading to activation of the FAS endodomain. The chimeric protein is useful as a suicide gene. The invention also provides a cell, such as a T cell comprising such a chimeric protein, which is useful in adoptive T cell immunotherapy approaches.
Claims21
A chimeric protein comprising a multi-spanning transmembrane protein fused to a FAS endodomain,
- wherein the multi-spanning transmembrane protein comprises CD20 truncated at the amino-terminus so that it lacks up to 41 amino acids from the CD20 amino-terminus, or at the carboxy-terminus so that it lacks up to 61 amino acids from the CD20 carboxy-terminus, and
- wherein the multi-spanning transmembrane protein binds at least one extracellular ligand selected from Rituxumab, Ofatumumab or Veltuzumab, leading to activation of the FAS endodomain.
A chimeric protein comprising a multi-spanning transmembrane protein that consists of the amino acid sequence of SEQ ID NO:
- 4, SEQ ID NO:
- 5, or SEQ ID NO:
- 6 fused to a FAS endodomain, wherein the multi-spanning transmembrane protein binds at least one extracellular ligand selected from Rituxumab, Ofatumumab or Veltuzumab, leading to activation of the FAS endodomain.
A chimeric protein comprising:
- a multi-spanning transmembrane protein fused to a FAS endodomain,
- wherein the multi-spanning transmembrane protein comprises the amino acid sequence of SEQ ID NO:
- 3 truncated at the amino terminus so that it lacks up to 41 amino acids from the amino-terminus of SEQ ID NO:
- 3, or truncated at the carboxy-terminus so that it lacks up to 61 amino acids from the carboxy-terminus of SEQ ID NO:
- 3, and optionally has one or both of the following substitution mutations:
- (a) an amino acid substitution at position A170 of SEQ ID NO:
- 3;
- (b) an amino acid substitution at position P172 of SEQ ID NO:
- 3;
- and
- wherein the multi-spanning transmembrane protein binds at least one extracellular ligand selected from Rituxumab, Ofatumumab or Veltuzumab, leading to activation of the FAS endodomain.
Dependencies are inferred from the claim text.