Anti-GCC antibody molecules and methods for use of same
View Patent ↗Antibodies and antigen-binding fragments of antibodies that bind GCC are disclosed. The invention also provides therapeutic and diagnostic methods utilizing the antibodies and antigen-binding fragments provided herein.
1. Isolated nucleic acid sequences that encode:
a) an anti-GCC antibody molecule, comprising
(i) a light chain variable region (SEQ ID NO: 13) and a heavy chain variable region (SEQ ID NO: 11) of antibody MIL-44-148-2; or
(ii) a light chain variable region (SEQ ID NO: 17) and a heavy chain variable region (SEQ ID NO: 15) of antibody MIL-44-67-4; or
b) an anti-GCC antibody molecule, comprising
(i) light chain CDR1 (SEQ ID NO: 27), CDR2 (SEQ ID NO: 28), and CDR3 (SEQ ID NO: 29), and heavy chain CDR1 (SEQ ID NO: 21), CDR2 (SEQ ID NO: 22), and CDR3 (SEQ ID NO: 23) of antibody MIL-44-148-2, or
(ii) light chain CDR1 (SEQ ID NO: 39), CDR2 (SEQ ID NO: 40), and CDR3 (SEQ ID NO: 41) and heavy chain CDR1 (SEQ ID NO: 33), CDR2 (SEQ ID NO: 34), and CDR3 (SEQ ID NO: 35) of antibody MIL-44-67-4.
2. A cell comprising the isolated nucleic acid sequences of claim 1 .
3. A method of producing an antibody molecule comprising culturing the cell of claim 2 under conditions that allow production of an antibody molecule, thereby producing:
a) an anti-GCC antibody molecule, comprising
(i) a light chain variable region (SEQ ID NO: 13) and a heavy chain variable region (SEQ ID NO: 11) of antibody MIL-44-148-2; or
(ii) a light chain variable region (SEQ ID NO: 17) and a heavy chain variable region (SEQ ID NO: 15) of antibody MIL-44-67-4; or
b) an anti-GCC antibody molecule, comprising
(i) light chain CDR1 (SEQ ID NO: 27), CDR2 (SEQ ID NO: 28), and CDR3 (SEQ ID NO: 29), and heavy chain CDR1 (SEQ ID NO: 21), CDR2 (SEQ ID NO: 22), and CDR3 (SEQ ID NO: 23) of antibody MIL-44-148-2, or
(ii) light chain CDR1 (SEQ ID NO: 39), CDR2 (SEQ ID NO: 40), and CDR3 (SEQ ID NO: 41) and heavy chain CDR1 (SEQ ID NO: 33), CDR2 (SEQ ID NO: 34), and CDR3 (SEQ ID NO: 35) of antibody MIL-44-67-4.
4. A vector comprising one or both of the light chain and heavy chain of:
a) an anti-GCC body molecule, comprising
(i) a light chain variable region (SEQ ID NO: 13) and a heavy chain variable region (SEQ ID NO: 11) of antibody MIL-44-148-2; or
(ii) a light chain variable region (SEQ ID NO: 17) and a heavy chain variable region (SEQ ID NO: 15) of antibody MIL-44-67-4; or
b) an anti-GCC antibody molecule, comprising
(i) light chain CDR1 (SEQ ID NO: 27), CDR2 (SEQ ID NO: 28), and CDR3 (SEQ ID NO: 29), and heavy chain CDR1 (SEQ ID NO: 21), CDR2 (SEQ ID NO: 22), and CDR3 (SEQ ID NO: 23) of antibody MIL-44-148-2, or
(ii) light chain CDR1 (SEQ ID NO: 39), CDR2 (SEQ ID NO: 40), and CDR3 (SEQ ID NO: 41) and heavy chain CDR1 (SEQ ID NO: 33), CDR2 (SEQ ID NO: 34), and CDR3 (SEQ ID NO: 35) of antibody MIL-44-67-4.
5. A method of detecting a GCC molecule comprising contacting the molecule with:
a) an anti-GCC body molecule, comprising
(i) a light chain variable region (SEQ ID NO: 13) and a heavy chain variable region (SEQ ID NO: 11) of antibody MIL-44-148-2; or
(ii) a light chain variable region (SEQ ID NO: 17) and a heavy chain variable region (SEQ ID NO: 15) of antibody MIL-44-67-4; or
b) an anti-GCC antibody molecule, comprising
(i) light chain CDR1 (SEQ ID NO: 27), CDR2 (SEQ ID NO: 28), and CDR3 (SEQ ID NO: 29), and heavy chain CDR1 (SEQ ID NO: 21), CDR2 (SEQ ID NO: 22), and CDR3 (SEQ ID NO: 23) of antibody MIL-44-148-2, or
(ii) light chain CDR1 (SEQ ID NO: 39), CDR2 (SEQ ID NO: 40), and CDR3 (SEQ ID NO: 41) and heavy chain CDR1 (SEQ ID NO: 33), CDR2 (SEQ ID NO: 34), and CDR3 (SEQ ID NO: 35) of antibody MIL-44-67-4.
6. The method of claim 5 , wherein said method comprises an immunohistochemistry assay using a biological sample derived from a patient suspected of having a GCC expressing cancer.
7. The method of claim 6 , wherein said biological sample is a tumor biopsy.
8. The method of claim 6 , further comprising the step of quantifying GCC expression in said biological sample.
9. The method of claim 8 , wherein said quantification of GCC expression comprises apical GCC expression, cytoplasmic GCC expression, or both.
10. The method of claim 8 , wherein said quantification step comprises an H-score approach.
11. The method of claim 6 , wherein said GCC expressing cancer is selected from the group consisting of: colorectal cancer, gastric cancer, esophageal cancer, pancreatic cancer, liver cancer, ovarian cancer, lung cancer, a gastrointestinal neuroendocrine tumor, and a bronchopulmonary neuroendocrine tumor.
12. A method of treating a patient having cancer characterized by GCC-expressing tumor cells, comprising:
a. detecting GCC expression on a sample of tumor cells from the patient by contacting said sample with;
(1) an anti-GCC antibody molecule, comprising
(i) a light chain variable region (SEQ ID NO: 13) and a heavy chain variable region (SEQ ID NO: 11) of antibody MIL-44-145-2; or
(ii) a light chain variable region (SEQ ID NO: 17) and a heavy chain variable region (SEQ ID NO: 15) of antibody MIL-44-67-4; or
(2) an anti-GCC antibody molecule, comprising
(i) light chain CDR1 (SEQ ID NO: 27), CDR2 (SEQ ID NO: 28), and CDR3 (SEQ ID NO: 29), and heavy chain CDR1 (SEQ ID NO: 21), CDR2 (SEQ ID NO: 22), and CDR3 (SEQ ID NO: 23) of antibody MIL-44-148-2, or
(ii) light chain CDR1 (SEQ ID NO: 39), CDR2 (SEQ ID NO: 40), and CDR3 (SEQ ID NO: 41) and heavy chain CDR1 (SEQ ID NO: 33), CDR2 (SEQ ID NO: 34), and CDR3 (SEQ ID NO: 35) of antibody MIL-44-67-4; and
b. administering a therapeutic anti-CGG antibody molecule conjugated to a toxin if the tumor cells express GCC on the cell surface.