Methods for treating pancreatic cancer
The present disclosure is directed to methods of treating pancreatic cancer in subject using cancer with antibodies that specifically bind to progastrin.
1. A method for treating pancreatic cancer in a subject, comprising administering to a human subject diagnosed with pancreatic cancer an amount of an anti-human progastrin (anti-hPG) antibody sufficient to provide therapeutic benefit, wherein said anti-hPG antibody is a C-terminal monoclonal antibody that binds to a C-terminal region of human progastrin polypeptide (hPG) wherein the anti-hPG antibody comprises:
(i) a heavy chain variable region in which CDR1 comprises the amino acid sequence of VH CDR 1.8 (SEQ ID NO:37), CDR2 comprises the amino acid sequence of VH CDR 2.8 (SEQ ID NO:41), and CDR3 comprises the amino acid sequence of VH CDR 3.8 MO ID NO:45), and a light chain variable region in which CDR1 comprises the amino acid sequence of VL CDR 1.8 (SEQ ID NO:49), CDR2 comprises the amino acid sequence of VL CDR 2.8 (SEQ ID NO:52), and CDR3 comprises the amino acid sequence of VL CDR 3.8 (SEQ ID NO:55); or
(ii) a heavy chain variable region in which CDR1 comprises the amino acid sequence of VH CDR 1.13 (SEQ ID NO:38), CDR2 comprises the amino acid sequence of VH CDR 2.13 (SEQ ID NO:42), and CDR3 comprises the amino acid sequence of VH CDR 3.13 (SEQ ID NO:46), and a light chain variable region in which CDR1 comprises the amino acid sequence of VL CDR 1.13 (SEQ ID NO:50), CDR2 comprises the amino acid sequence of VL CDR 2.13 (SEQ ID NO:53), and CDR3 comprises the amino acid sequence of VL CDR 3.13 (SEQ ID NO:56).
2. The method of claim 1 in which the anti-hPG antibody is humanized.
3. The method of claim 1 in which the C-terminal anti-hPG monoclonal antibody competes for binding hPG with a reference antibody selected from:
(a) a monoclonal antibody comprising a heavy chain variable domain sequence of SEQ ID NO:59 and a light chain variable domain sequence of SEQ ID NO:63; and
(b) a monoclonal antibody comprising a heavy chain variable domain sequence of SEQ ID NO:60 and a light chain variable domain sequence of SEQ ID NO:64.
4. The method of claim 1 in which the pancreatic cancer is primary pancreatic cancer.
5. The method of claim 1 in which the pancreatic cancer is metastatic pancreatic cancer.
6. The method of claim 1 in which the anti-hPG monoclonal antibody is administered adjunctive to surgical resection of the tumor.
7. The method of claim 1 in which the anti-hPG monoclonal antibody is administered adjunctive to chemotherapy.
8. A method of inhibiting proliferation of a pancreatic tumor cell comprising exposing the cell to an amount of an anti-human progastrin (anti-hPG) antibody sufficient to inhibit its proliferation, wherein said anti-hPG antibody is a C-terminal monoclonal antibody that binds to a C-terminal region of human progastrin polypeptide,
wherein the anti-hPG antibody comprises:
(i) a heavy chain variable region in which CDR1 comprises the amino acid sequence of VH CDR 1.8 (SEQ ID NO:37), CDR2 comprises the amino acid sequence of VH CDR 2.8 (SEQ ID NO:41), and CDR3 comprises the amino acid sequence of VH CDR 3.8 (SEQ ID NO:45), and a light chain variable region in which CDR1 comprises the amino acid sequence of VL CDR 1.8 (SEQ ID NO:49), CDR2 comprises the amino acid sequence of VL CDR 2.8 (SEQ ID NO:52), and CDR3 comprises the amino acid sequence of VL CDR 3.8 (SEQ ID NO:55); or
(ii) a heavy chain variable region in which CDR1 comprises the amino acid sequence of VH CDR 1.13 (SEQ ID NO:38), CDR2 comprises the amino acid sequence of VH CDR 2.13 (SEQ ID NO:42), and CDR3 comprises the amino acid sequence of VH CDR 3.13 (SEQ ID NO:46), and a light chain variable region in which CDR1 comprises the amino acid sequence of VL CDR 1.13 (SEQ ID NO:50), CDR2 comprises the amino acid sequence of VL CDR 2.13 (SEQ ID NO:53), and CDR3 comprises the amino acid sequence of VL CDR 3.13 (SEQ ID NO:56).
9. The method of claim 8 in which is practiced in vitro.
10. The method of claim 8 which is practiced in vivo.