Cell
The present invention provides a cell which comprises; (i) a chimeric antigen receptor (CAR) or a transgenic T-cell receptor (TCR); and (ii) a polypeptide capable of co-localizing a beta-2 microglobulin component of a MHC class I molecule with an intracellular signalling domain within the cell.
1. A cell which comprises: (i) a chimeric antigen receptor (CAR) or a transgenic T-cell receptor (TCR), and (ii) a polypeptide capable of co-localizing a beta-2 microglobulin (B2M) component of a major histocompatibility complex (MHC) class I molecule with an intracellular signalling domain within the cell, wherein the polypeptide comprises: (a) a B2M component fused to a transmembrane domain and a CD3 zeta endodomain, (b) a B2M component linked to a component of the CD3/TCR complex, or (c) a B2M-TCR bispecific construct comprising a first binding component which recognizes B2M and a second binding component which recognizes the CD3/TCR complex, and wherein the intracellular signalling domain comprises a CD3 zeta endodomain.
2. A cell according to claim 1 , wherein the polypeptide comprises a B2M component fused to a transmembrane domain and a CD3 zeta endodomain.
3. A cell according to claim 1 , wherein the polypeptide comprises a B2M component linked to a component of the CD3/TCR complex.
4. A cell according to claim 1 , wherein the polypeptide comprises a B2M-TCR bispecific construct comprising a first binding component which recognizes B2M and a second binding component which recognizes the CD3/TCR complex.
5. A nucleic acid construct formulated for being introduced into a cell which comprises: (i) a first nucleic acid sequence which encodes a chimeric antigen receptor (CAR) or a transgenic TCR; and (ii) a second nucleic acid sequence which encodes a polypeptide capable of co-localizing a beta-2 microglobulin (B2M) component of a major histocompatibility complex (MHC) class I molecule with an intracellular signalling domain, wherein the polypeptide comprises: (a) a B2M component fused to a transmembrane domain and a CD3 zeta endodomain, (b) a B2M component linked to a component of the CD3/TCR complex, or (c) a B2M-TCR bispecific construct comprising a first binding component which recognizes the B2M and a second binding component which recognizes the CD3/TCR complex, and wherein the intracellular signalling domain comprises a CD3 zeta endodomain.
6. A vector which comprises a nucleic acid construct according to claim 5 .
7. A kit comprising the vector of claim 6 .
8. A pharmaceutical composition which comprises a plurality of cells according to claim 1 .
9. A method for treating and/or preventing a disease, which comprises the step of administering a pharmaceutical composition according to claim 8 to a subject in need thereof.
10. The method according to claim 9 wherein the cell is autologous.
11. The method according to claim 9 wherein the cell is allogenic.
12. The method according to claim 9 , wherein the disease is immune rejection of the cell.
13. A method for making a cell according to claim 1 , which comprises the step of introducing into the cell: (i) a first nucleic acid sequence which encodes the chimeric antigen receptor (CAR) or the transgenic TCR; and (ii) a second nucleic acid sequence which encodes the polypeptide.