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US 11,242,377 B2Granted
Chimeric receptor with ligand binding exodomain and cytokine and T cell signalling endodomains
AssigneeAutolus Limited
InventorsMartin Pulé, Shaun Cordoba, Matteo Righi
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Abstract
The present invention provides a chimeric receptor which comprises: a ligand-binding exodomain; and an endodomain which comprises: (i) a cytokine receptor endodomain; and (ii) an intracellular T cell signalling domain.
Claims35
A chimeric receptor system which comprises a first chimeric receptor and a second chimeric receptor, wherein the first and the second chimeric receptors each comprise:
- a ligand-binding exodomain that comprises an antigen binding domain of an antibody;
- a transmembrane domain;
- and
- an endodomain which comprises:
- (i) a cytokine receptor endodomain;
- and
- (ii) an intracellular T cell signalling domain,
- wherein the ligand is a tumour-secreted factor or a tumour cell surface antigen;
- wherein the cytokine receptor endodomain of the first chimeric receptor comprises or consists of IL-2 receptor β-chain endodomain or IL-7 receptor α-chain endodomain;
- wherein the cytokine receptor endodomain of the second chimeric receptor comprises or consists of common γ-chain receptor endodomain;
- and
- wherein the intracellular T cell signaling domain of the first chimeric receptor or the intracellular T cell signaling domain of the second chimeric receptor includes a CD3 zeta endodomain.
9 more elements
A chimeric receptor system comprising a chimeric receptor and an intracellular fusion protein,
- wherein the chimeric receptor comprises a ligand-binding exodomain that comprises an antigen binding domain of an antibody;
- a transmembrane domain;
- and an endodomain which comprises:
- (i) a cytokine receptor endodomain;
- and (ii) an intracellular T cell signalling domain, said intracellular T cell signaling domain comprising a CD3 zeta endodomain;
- wherein the intracellular fusion protein comprises a cytokine receptor endodomain and a ZAP70 SH2 domain;
- and
- wherein the cytokine receptor endodomain of the chimeric receptor is complementary to the cytokine receptor endodomain of the intracellular fusion protein, one of said endodomains comprising or consisting of an IL-2 receptor β-chain endodomain or IL-7 receptor α-chain endodomain, and the other of said endodomains comprising or consisting of a common γ-chain receptor endodomain.
5 more elements
A chimeric receptor system comprising a chimeric receptor and a transmembrane protein,
- wherein the chimeric receptor comprises a ligand-binding exodomain that comprises an antigen binding domain of an antibody;
- a transmembrane domain;
- and an endodomain which comprises:
- (i) a cytokine receptor endodomain;
- and (ii) an intracellular T cell signalling domain, said intracellular T cell signaling domain comprising a CD3 zeta endodomain;
- wherein the transmembrane protein lacks a ligand-binding exodomain, and comprises a cytokine receptor endodomain and a ZAP70 SH2 domain;
- and
- wherein the cytokine receptor endodomain of the chimeric receptor is complementary to the cytokine receptor endodomain of the transmembrane protein, one of said endodomains comprising or consisting of an IL-2 receptor β-chain endodomain or IL-7 receptor α-chain endodomain, and the other of said endodomains comprising or consisting of a common γ-chain receptor endodomain.
5 more elements
Dependencies are inferred from the claim text.