Methods for treating colorectal cancer
The present disclosure is directed to methods of treating and preventing colorectal cancer metastasis or recurrence of colorectal cancer with compositions comprising anti-progastrin antibodies.
1. A method for treating metastatic colorectal cancer, comprising the step of administering to a human patient in need of treatment for metastatic colorectal cancer a therapeutically effective amount of a composition comprising an anti-hPG antibody, wherein said anti-hPG antibody is a monoclonal antibody that binds to human progastrin polypeptide (hPG) having an amino acid sequence of SEQ ID NO:101 but does not detectably bind to an amidated gastrin 17 consisting of SEQ ID NO:104, a glycine-extended gastrin 17 consisting of SEQ ID NO:105, or C-terminal Flanking Peptide (CTFP) consisting of SEQ ID NO:106, in which the anti-hPG antibody is a C-terminal anti-hPG antibody.
2. The method of claim 1 in which the C-terminal anti-hPG monoclonal antibody is raised against an immunogen comprising a peptide having the sequence QGPWLEEEEEAYGWMDFGRRSAEDEN (SEQ ID NO:27).
3. The method of claim 1 in which the C-terminal anti-hPG monoclonal antibody competes for binding to 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;
(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 , wherein the C-terminal anti-hPG antibody binds an epitope in a C-terminal epitope region of hPG comprising the amino acid sequence of SEQ ID NO:33.
5. The method of claim 1 , wherein the C-terminal anti-hPG antibody binds an epitope in a C-terminal epitope region of hPG comprising the amino acid sequence of SEQ ID NO:34.
6. The method of claim 1 , wherein the C-terminal anti-hPG antibody binds an epitope in a C-terminal epitope region of hPG comprising the amino acid sequence of SEQ ID NO:35.
7. The method of claim 1 , wherein the C-terminal anti-hPG antibody binds an epitope in a C-terminal epitope region of hPG comprising the amino acid sequence of SEQ ID NO:36.
8. The method of claim 1 , wherein said anti-hPG monoclonal antibody comprises a heavy chain variable region in which CDR1 comprises the amino acid sequence of V H CDR 1.8 (SEQ ID NO:37), CDR2 comprises the amino acid sequence of V H CDR 2.8 (SEQ ID NO:41), and CDR3 comprises the amino acid sequence of V H CDR 3.8 (SEQ ID NO:45), and a light chain variable region in which CDR1 comprises the amino acid sequence of V L CDR 1.8 (SEQ ID NO:49), CDR2 comprises the amino acid sequence of V L CDR 2.8 (SEQ ID NO:52), and CDR3 comprises the amino acid sequence of V L CDR 3.8 (SEQ ID NO:55).
9. The method of claim 1 , wherein said anti-hPG monoclonal antibody comprises a heavy chain variable region in which CDR1 comprises the amino acid sequence of V H CDR 1.13 (SEQ ID NO:38), CDR2 comprises the amino acid sequence of V H CDR 2.13 (SEQ ID NO:42), and CDR3 comprises the amino acid sequence of V H CDR 3.13 (SEQ ID NO:46), and a light chain variable region in which CDR1 comprises the amino acid sequence of V L CDR 1.13 (SEQ ID NO:50), CDR2 comprises the amino acid sequence of V L CDR 2.13 (SEQ ID NO:53), and CDR3 comprises the amino acid sequence of V L CDR 3.13 (SEQ ID NO:56).