Method of eliminating hematopoietic stem cells/hematopoietic progenitors (HSC/HP) in a patient using bi-specific antibodies
The described invention provides compositions containing bi-specific antibodies that bind to human tyrosine kinase receptor FLT3/FLK2 receptor protein and to CD3 receptor protein expressed on T-cells and use of the compositions containing the bispecific antibodies in the preparation of a medicament for eliminating hematopoietic stem cells/hematopoietic progenitors (HSC/HP) in a patient.
1. A monoclonal antibody or an antigen binding fragment thereof that binds to a human FLT3/FLK2 receptor, wherein the monoclonal antibody or the antigen binding fragment thereof comprises a light chain binding region and a heavy chain binding region, wherein the light chain binding region comprises SEQ ID NO: 5 and the heavy chain binding region comprises SEQ ID NO: 7.
2. The monoclonal antibody or antigen binding fragment thereof according to claim 1 , wherein a half maximal effective concentration (EC50) of the monoclonal antibody or antigen binding fragment thereof is between 1 ng/mL (6.25 pM) and 2,000 ng/mL (12.5 nM).
3. The monoclonal antibody or antigen binding fragment thereof according to claim 2 , wherein the half maximal effective concentration (EC50) of the monoclonal antibody or antigen binding fragment thereof is between 10 ng/mL (62.5 pM) and 200 ng/mL (1.25 nM).
4. The monoclonal antibody or antigen binding fragment thereof according to claim 3 , wherein FLT3 antibody binding to human FLT3/FLK2 receptor protein on a cell is effective for the cell to internalize the bound antibody or antigen binding fragment.
5. A monoclonal antibody or an antigen binding fragment thereof that binds to a human FLT3/FLK2 receptor, wherein the monoclonal antibody or the antigen binding fragment thereof comprises a light chain binding region and a heavy chain binding region, wherein the light chain binding region comprises SEQ ID NO: 9 and the heavy chain binding region comprises SEQ ID NO: 11.
6. The monoclonal antibody or antigen binding fragment thereof according to claim 5 , wherein a half maximal effective concentration (EC50) of the monoclonal antibody or antigen binding fragment thereof is between 1 ng/mL (6.25 pM) and 2,000 ng/mL (12.5 nM).
7. The monoclonal antibody or antigen binding fragment thereof according to claim 6 , wherein the half maximal effective concentration (EC50) of the monoclonal antibody or antigen binding fragment thereof is between 10 ng/mL (62.5 pM) and 200 ng/mL (1.25 nM).
8. The monoclonal antibody or antigen binding fragment thereof according to claim 7 , wherein FLT3 antibody binding to human FLT3/FLK2 receptor protein on a cell is effective for the cell to internalize the bound antibody or antigen binding fragment.
9. A monoclonal antibody or an antigen binding fragment thereof that binds to a human FLT3/FLK2 receptor, wherein the monoclonal antibody or the antigen binding fragment thereof comprises a light chain binding region and a heavy chain binding region, wherein the light chain binding region comprises SEQ ID NO: 13 and the heavy chain binding region comprises SEQ ID NO: 15.
10. The monoclonal antibody or antigen binding fragment thereof according to claim 9 , wherein a half maximal effective concentration (EC50) of the monoclonal antibody or antigen binding fragment thereof is between 1 ng/mL (6.25 pM) and 2,000 ng/mL (12.5 nM).
11. The monoclonal antibody or antigen binding fragment thereof according to claim 10 , wherein the half maximal effective concentration (EC50) of the monoclonal antibody or antigen binding fragment thereof is between 10 ng/mL (62.5 pM) and 200 ng/mL (1.25 nM).
12. The monoclonal antibody or antigen binding fragment thereof according to claim 11 , wherein FLT3 antibody binding to human FLT3/FLK2 receptor protein on a cell is effective for the cell to internalize the bound antibody or antigen binding fragment.
13. A monoclonal antibody or an antigen binding fragment thereof that binds to a human FLT3/FLK2 receptor, wherein the monoclonal antibody or the antigen binding fragment thereof comprises a light chain binding region and a heavy chain binding region, wherein the light chain binding region comprises SEQ ID NO: 17 and the heavy chain binding region comprises SEQ ID NO: 19.
14. The monoclonal antibody or antigen binding fragment thereof according to claim 13 , wherein a half maximal effective concentration (EC50) of the monoclonal antibody or antigen binding fragment thereof is between 1 ng/mL (6.25 pM) and 2,000 ng/mL (12.5 nM).
15. The monoclonal antibody or antigen binding fragment thereof according to claim 14 , wherein the half maximal effective concentration (EC50) of the monoclonal antibody or antigen binding fragment thereof is between 10 ng/mL (62.5 pM) and 200 ng/mL (1.25 nM).
16. The monoclonal antibody or antigen binding fragment thereof according to claim 15 , wherein FLT3 antibody binding to human FLT3/FLK2 receptor protein on a cell is effective for the cell to internalize the bound antibody or antigen binding fragment.