Methods for treating cancer or modulating T cells or NK cells in a subject by administering cells comprising chimeric transmembrane proteins
AssigneeAutolus Limited
InventorsMartin Pulé, Shaun Cordoba, Matteo Righi, James Sillibourne, Shimobi Onuoha, Simon Thomas
Life of this patent
Estimating the term…
Abstract
The present invention provides a chimeric cytokine receptor (CCR) comprising: (i) an exodomain which binds to a ligand selected from a tumour secreted factor, a chemokine and a cell-surface antigen; and (ii) a cytokine receptor endodomain.
Claims11
A method for treating a subject for cancer, which comprises the step of administering a pharmaceutical composition to the subject, said pharmaceutical composition comprising a plurality of cells, said cells comprising a chimeric transmembrane protein and a chimeric antigen receptor (CAR),
- (A) wherein said chimeric transmembrane protein comprises:
- (i) a first polypeptide which comprises
- (a) a first dimerization domain comprising the dimerization portion of an antibody heavy chain constant domain (CH) and
- (b) a first chain of a cytokine receptor endodomain;
- and
- (ii) a second polypeptide which comprises
- (a) a second dimerization domain comprising the dimerization portion of an antibody light chain constant domain (CL), which dimerizes with the first dimerization domain and
- (b) a second chain of the cytokine-receptor endodomain,
- wherein one of the first and second chains of the cytokine receptor endodomain comprises an IL-2 receptor β-chain endodomain, an IL-7 receptor α-chain endodomain, or an IL-15 receptor α-chain endodomain, and wherein the other of the first and second chains of the cytokine receptor endodomain comprises a γ-chain receptor endodomain that is common to the IL-2, IL-7, and IL-15 receptors;
- and
- wherein the first and second polypeptides spontaneously dimerize;
- and
- (B) wherein the CAR comprises an antigen-binding domain, a spacer domain, a transmembrane domain, and an endodomain, wherein the antigen-binding domain specifically binds a tumour-associated antigen (TAA).
A method for modulating a T cell or NK cell response in a subject, the method comprising administering a pharmaceutical composition to the subject, said pharmaceutical composition comprising a plurality of T cells or NK cells, said cells comprising a chimeric transmembrane protein, said chimeric transmembrane protein comprising:
- (i) a first polypeptide which comprises
- (a) a first dimerization domain comprising the dimerization portion of an antibody heavy chain constant domain (CH) and
- (b) a first chain of a cytokine receptor endodomain;
- and
- (ii) a second polypeptide which comprises
- (a) a second dimerization domain comprising the dimerization portion of an antibody light chain constant domain (CL), which dimerizes with the first dimerization domain and
- (b) a second chain of the cytokine-receptor endodomain,
- wherein one of the first and second chains of the cytokine receptor endodomain comprises an IL-2 receptor β-chain endodomain, an IL-7 receptor α-chain endodomain, or an IL-15 receptor α-chain endodomain, and wherein the other of the first and second chains of the cytokine receptor endodomain comprises a γ-chain receptor endodomain that is common to the IL-2, IL-7, and IL-15 receptors;
- and
- wherein the first and second polypeptides spontaneously dimerize.
Dependencies are inferred from the claim text.