Recombinant tumor specific antibody and use thereof
View Patent ↗The invention provides a family of antibodies that specifically bind the human epithelial cell adhesion molecule. The antibodies comprise modified variable regions, more specially, modified framework regions, which reduce their immunogenicity when administered to a human. The antibodies, when coupled to the appropriate moiety, may be used in the diagnosis, prognosis and treatment of cancer.
1. A nucleic acid encoding an anti-EpCAM protein comprising an antibody that binds human EpCAM and that comprises:
(a) an immunoglobulin light chain variable region comprising: (i) amino acid residues 24-31 of SEQ ID NO: 1; (ii) amino acid residues 49-55 of SEQ ID NO: 1; and (iii) amino acid residues 88-96 of SEQ ID NO: 1; and
(b) an amino acid sequence defining an immunoglobulin light chain framework region selected from the group consisting of: (i) amino acid residues 1-23 of SEQ ID NO:8; and (ii) amino acid residues 1-23 of SEQ ID NO:9.
2. The nucleic acid of claim 1 , wherein the antibody comprises amino acids 1-106 of SEQ ID NO:9.
3. The nucleic acid of claim 1 , wherein the antibody has a Kd for EpCAM of at least 10 −8 M.
4. The nucleic acid of claim 1 , wherein the protein comprises a cytokine.
5. The nucleic acid of claim 4 , wherein the cytokine is IL-2.
6. A cell comprising the nucleic acid of claim 1 .
7. A nucleic acid encoding an anti-EpCAM protein, wherein the protein comprises an antibody that binds human EpCAM and that comprises:
(a) an immunoglobulin heavy chain variable region comprising: (i) amino acid residues 26-35 of SEQ ID NO:2; (ii) amino acid residues 50-62 of SEQ ID NO:2; and (iii) amino acid residues 101-105 of SEQ ID NO:2; and
(b) an amino acid sequence defining an immunoglobulin heavy chain framework region selected from the group consisting of: (i) amino acid residues 1-25 of SEQ ID NO: 18; and (ii) amino acid residues 67-98 of SEQ ID NO: 18.
8. The nucleic acid of claim 7 , wherein the antibody comprises amino acids 1-116 of SEQ ID NO:18.
9. The nucleic acid of claim 7 , wherein the antibody has a Kd for EpCAM of at least 10 −8 M.
10. The nucleic acid of claim 7 , wherein the protein comprises a cytokine.
11. The nucleic acid of claim 10 , wherein the cytokine is IL-2.
12. A cell comprising the nucleic acid of claim 7 .
13. A nucleic acid encoding an anti-EpCAM protein, wherein the protein comprises an antibody that binds human EpCAM and that comprises an antibody light chain variable region comprising an amino acid sequence defined by residues 1-106 of SEQ ID NO:9 and an antibody heavy chain variable region comprising an amino acid sequence defined by residues 1-116 of SEQ ID NO: 18.
14. The nucleic acid of claim 13 , wherein the protein comprises a cytokine.
15. The nucleic acid of claim 14 , wherein the cytokine is IL-2.
16. A cell comprising the nucleic acid of claim 13 .
17. A nucleic acid encoding a humanized or deimmunized anti-EpCAM protein suitable for administering into a human patient for treating a disease associated with EpCAM over-expression, wherein the protein comprises an antibody that binds human EpCAM and that comprises:
(a) an immunoglobulin light chain variable region comprising: (i) amino acid residues 24-31 of SEQ ID NO: 1; (ii) amino acid residues 49-55 of SEQ ID NO: 1; and (iii) amino acid residues 88-96 of SEQ ID NO: 1; and
(b) an amino acid sequence defining an immunoglobulin light chain framework region selected from the group consisting of: (i) amino acid residues 1-23 of SEQ ID NO:8; and (ii) amino acid residues 1-23 of SEQ ID NO:9.
18. A nucleic acid encoding a humanized or deimmunized anti-EpCAM protein suitable for administering into a human patient for treating a disease associated with EpCAM over-expression, wherein the protein comprises an antibody that binds human EpCAM and that comprises:
(a) an immunoglobulin heavy chain variable region comprising: (i) amino acid residues 26-35 of SEQ ID NO:2; (ii) amino acid residues 50-62 of SEQ ID NO:2; and (iii) amino acid residues 101-105 of SEQ ID NO:2; and
(b) an amino acid sequence defining an immunoglobulin heavy chain framework region selected from the group consisting of: (i) amino acid residues 1-25 of SEQ ID NO: 18; and (ii) amino acid residues 67-98 of SEQ ID NO: 18.
19. A nucleic acid encoding a humanized or deimmunized anti-EpCAM protein suitable for administering into a human patient for treating a disease associated with EpCAM over-expression, wherein the protein comprises an antibody that binds human EpCAM and that comprises an antibody light chain variable region comprising an amino acid sequence defined by residues 1-106 of SEQ ID NO:9 and an antibody heavy chain variable region comprising an amino acid sequence defined by residues 1-116 of SEQ ID NO:18.