Biological materials and uses thereof
The invention provides binding molecules, including antibody molecules which selectively bind to a cell surface antigen of a target cell, and wherein the binding molecules, on binding the cell surface antigen, induce apoptosis of the target cell. There is also provided methods of and pharmaceutical compositions for apoptosis induction and uses thereof.
1. An isolated human antibody molecule that selectively binds to cell surface ICAM-1 on a target cell and, on binding ICAM-1, induces apoptosis.
2. The antibody molecule as claimed in claim 1 wherein the target cell is an immune cell or an epithelial cell.
3. The antibody molecule as claimed in claim 2 wherein the immune cell is a B lymphocyte.
4. The antibody molecule as claimed in claim 1 wherein the target cell is associated with a disease.
5. The antibody molecule as claimed in claim 4 wherein the disease is selected from the group consisting of: cancer; autoimmune diseases including but not restricted to rheumatoid arthritis and SLE, acute and chronic inflammatory disorders, sepsis and infectious disease including but not restricted to HIV.
6. The antibody molecule as claimed in claim 5 wherein the disease is a cancer selected from lymphoma, leukaemia, myeloma, gastric cancer, breast cancer, liver cancer, lung cancer, melanoma, bladder cancer, choroid cancer, pancreatic cancer, colon cancer and prostate cancer.
7. The antibody molecule as claimed in claim 1 wherein the antibody molecule is an IgG.
8. The antibody molecule as claimed in claim 7 wherein the antibody is a single chain antibody selected from the group of an IgG 1 , IgG 2 , IgG 3 or IgG 4 .
9. The antibody molecule as claimed in claim 1 wherein the antibody has variable regions having the sequences of SEQ ID NO:6 and SEQ ID NO:8, or derivatives thereof.
10. A pharmaceutical composition comprising a human antibody molecule and a pharmaceutically-acceptable carrier, excipient or diluent, wherein said antibody molecule selectively binds to cell surface ICAM-1 of a target cell and, on binding ICAM-1, induces apoptosis of the target cell.
11. The antibody molecule of claim 1 , wherein the antibody molecule selectively binds cell surface ICAM-1 and, on binding ICAM-1, induces apoptosis of a target cell in vitro.
12. The pharmaceutical composition of claim 10 , wherein the antibody molecule selectively binds cell surface ICAM-1 and, on binding ICAM-1, induces apoptosis of a target cell in vitro.
13. A method of inducing apoptosis in a target cell comprising the steps:
a. providing one or more target cells displaying the cell surface antigen ICAM-1;
b. providing an isolated human antibody molecule which selectively binds to cell surface ICAM-1 and, on binding ICAM-1, induces apoptosis of the target cell; and
c. exposing the target cells of (a) to the antibody molecule of (b) to induce apoptosis in the target cells.
14. An in vitro method of inducing apoptosis in a target cell comprising the steps of:
a. providing one or more target cells;
b. providing an isolated human antibody molecule that selectively binds to cell surface ICAM-1 of said target cells and, on binding ICAM-1, induces apoptosis of the target cells; and
c. exposing the target cells of (a) to the antibody molecule of (b) so as to induce apoptosis in the target cells.
15. An in vitro method as claimed in claim 14 wherein the target cells provided in step (a) are immune cells or epithelial cells.
16. An in vitro method as claimed in claim 15 wherein the immune cells are B-lymphocytes.
17. An in vitro method as claimed in claim 14 wherein the target cells are associated with a disease.
18. An in vitro method as claimed in claim 17 wherein the disease is selected from the group consisting of: cancer; autoimmune diseases including but not restricted to rheumatoid arthritis and SLE, acute and chronic inflammatory disorders, sepsis and infectious disease including but not restricted to HIV.
19. An in vitro method as claimed in claim 18 wherein the disease is a cancer selected from lymphoma, leukaemia, myeloma, gastric cancer, breast cancer, liver cancer, lung cancer, melanoma, bladder cancer, choroid cancer, colon cancer, and prostate cancer.
20. An in vivo method of inducing apoptosis in a target cell comprising the steps of:
a. providing one or more target cells;
b. providing an isolated human antibody molecule that selectively binds to cell surface ICAM-1 of said target cells and, on binding ICAM-1, induces apoptosis of the target cells; and
c. exposing the target cells of (a) to the antibody molecule of (b) so as to induce apoptosis in the target cells.
21. An in vivo method as claimed in claim 20 wherein the target cells provided in step (a) are immune cells or epithelial cells.
22. An in vivo method as claimed in claim 21 wherein the immune cells are B-lymphocytes.
23. An in vivo method as claimed in claim 20 wherein the target cells are associated with a disease.
24. An in vivo method as claimed in claim 23 wherein the disease is selected from the group consisting of: cancer; autoimmune diseases including but not restricted to rheumatoid arthritis and SLE, acute and chronic inflammatory disorders, sepsis and infectious disease including but not restricted to HIV.
25. An in vivo method as claimed in claim 24 wherein the disease is a cancer selected from lymphoma, leukaemia, myeloma, gastric cancer, breast cancer, liver cancer, lung cancer, melanoma, bladder cancer, choroid cancer, pancreatic cancer, colon cancer and prostate cancer.