Methods for treating cancer by administering humanized pan-HER antibody compositions
The invention relates to humanized recombinant antibodies targeting the EGFR family receptors EGFR, HER2 and HER3, compositions comprising at least one humanized anti-EGFR antibody, at least one humanized anti-HER2 antibody and at least one humanized anti-HER3 antibody, and use of the antibody compositions for treatment of cancer. The invention also relates to the use of antibodies targeting multiple EGFR-family receptors to treat cancer (e.g., pancreatic cancer) and cancer that has acquired resistance to previous therapies.
1. A method for treating cancer in a human patient, the method comprising administering to said patient an effective amount of an antibody composition comprising:
a) an anti-epidermal growth factor receptor (EGFR) antibody comprising a heavy chain and a light chain that comprise the amino acid sequences of:
SEQ ID NOs: 42 and 43, respectively,
SEQ ID NOs: 38 and 39, respectively,
SEQ ID NOs: 40 and 41, respectively,
SEQ ID NOs: 44 and 45, respectively, or
SEQ ID NOs: 46 and 47, respectively;
b) an anti-human epidermal growth factor receptor 2 (HER2) antibody comprising a heavy chain and a light chain that comprise the amino acid sequences of:
SEQ ID NOs: 50 and 51, respectively,
SEQ ID NOs: 48 and 49, respectively, or
SEQ ID NOs: 52 and 53, respectively; and
c) an anti-human epidermal growth factor receptor 3 (HER3) antibody comprising a heavy chain and a light chain that comprise the amino acid sequences of:
SEQ ID NOs: 54 and 55, respectively,
SEQ ID NOs: 56 and 57, respectively,
SEQ ID NOs: 58 and 59, respectively, or
SEQ ID NOs: 60 and 61, respectively.
2. The method of claim 1 , wherein said antibody composition comprises:
a) an anti-epidermal growth factor receptor (EGFR) antibody comprising a heavy chain and a light chain that comprise the amino acid sequences of:
SEQ ID NOs: 38 and 39, respectively,
SEQ ID NOs: 40 and 41, respectively, or
SEQ ID NOs: 42 and 43, respectively;
b) an anti-EGFR antibody comprising a heavy chain and a light chain that comprise the amino acid sequences of:
SEQ ID NOs: 44 and 45, respectively, or
SEQ ID NOs: 46 and 47, respectively;
c) an anti-human epidermal growth factor receptor 2 (HER2) antibody comprising a heavy chain and a light chain that comprise the amino acid sequences of:
SEQ ID NOs: 48 and 49, respectively, or
SEQ ID NOs: 50 and 51, respectively;
d) an anti-HER2 antibody comprising a heavy chain that comprises the amino acid sequence of SEQ ID NO: 52 and a light chain that comprises the amino acid sequence of SEQ ID NO: 53;
e) an anti-human epidermal growth factor receptor 3 (HER3) antibody comprising a heavy chain and a light chain that comprise the amino acid sequences of:
SEQ ID NOs: 54 and 55, respectively, or
SEQ ID NOs: 56 and 57, respectively; and
f) an anti-HER3 antibody comprising a heavy chain and a light chain that comprise the amino acid sequences of:
SEQ ID NOs: 58 and 59, respectively, or
SEQ ID NOs: 60 and 61, respectively.
3. The method of claim 1 , wherein said antibody composition has at least one of the following properties:
a) inhibits cancer growth in the patient;
b) reduces EGFR, HER2, or HER3 expression in cancer cells in the patient; and
c) prevents EGFR, HER2, or HER3 up-regulation in cancer cells in the patient.
4. The method of claim 1 , wherein the patient has pancreatic cancer, lung cancer, head and neck cancer, breast cancer, gastric cancer, colorectal cancer, esophageal cancer, or ovarian cancer.
5. The method of claim 1 , wherein the patient has pancreatic cancer and a KRAS mutation.
6. The method of claim 1 , wherein at least one of the antibodies is conjugated to an anti-cancer agent.
7. The method of claim 1 , wherein the patient has been treated for cancer previously.
8. The method of claim 1 , wherein said patient has acquired resistance to treatment with an antibody and/or a tyrosine kinase inhibitor.
9. The method of claim 8 , wherein the antibody is cetuximab, trastuzumab, or pertuzumab.
10. A method for treating cancer in a human patient, the method comprising administering to said patient an effective amount of an antibody composition comprising:
a) an anti-epidermal growth factor receptor (EGFR) antibody comprising the heavy chain variable region (VH) amino acid sequence of SEQ ID NO: 42 and the light chain variable region (VL) amino acid sequence of SEQ ID NO: 43;
b) an anti-EGFR antibody comprising the VH amino acid sequence of SEQ ID NO: 46 and the VL amino acid sequence of SEQ ID NO: 47;
c) an anti-human epidermal growth factor receptor 2 (HER2) antibody comprising the VH amino acid sequence of SEQ ID NO: 50 and the VL amino acid sequence of SEQ ID NO: 51;
d) an anti-HER2 antibody comprising the VH amino acid sequence of SEQ ID NO: 52 and the VL amino acid sequence of SEQ ID NO: 53;
e) an anti-human epidermal growth factor receptor 3 (HER3) antibody comprising the VH amino acid sequence of SEQ ID NO: 54 and the VL amino acid sequence of SEQ ID NO: 55; and
f) an anti-HER3 antibody comprising the VH amino acid sequence of SEQ ID NO: 60 and the VL amino acid sequence of SEQ ID NO: 61.
11. The method of claim 10 , wherein said antibody composition has at least one of the following properties:
a) inhibits cancer growth in the patient;
b) reduces EGFR, HER2, or HER3 expression in cancer cells in the patient; and
c) prevents EGFR, HER2, or HER3 up-regulation in cancer cells in the patient.
12. The method of claim 10 , wherein the patient has pancreatic cancer, lung cancer, head and neck cancer, breast cancer, gastric cancer, colorectal cancer, esophageal cancer, or ovarian cancer.
13. The method of claim 10 , wherein the patient has pancreatic cancer and a KRAS mutation.
14. The method of claim 10 , wherein at least one of the antibodies is conjugated to an anti-cancer agent.
15. The method of claim 10 , wherein the patient has been treated for cancer previously.
16. The method of claim 10 , wherein said patient has acquired resistance to treatment with an antibody and/or a tyrosine kinase inhibitor.
17. The method of claim 16 , wherein the antibody is cetuximab, trastuzumab, or pertuzumab.
18. A method for treating a human patient with a disorder characterized by overexpression of EGFR, HER2, and/or HER3, the method comprising administering to said patient an effective amount of an antibody composition comprising:
a) an anti-epidermal growth factor receptor (EGFR) antibody comprising a heavy chain and a light chain that comprise the amino acid sequences of:
SEQ ID NOs: 42 and 43, respectively,
SEQ ID NOs: 38 and 39, respectively,
SEQ ID NOs: 40 and 41, respectively,
SEQ ID NOs: 44 and 45, respectively, or
SEQ ID NOs: 46 and 47, respectively;
b) an anti-human epidermal growth factor receptor 2 (HER2) antibody comprising a heavy chain and a light chain that comprise the amino acid sequences of:
SEQ ID NOs: 50 and 51, respectively,
SEQ ID NOs: 48 and 49, respectively, or
SEQ ID NOs: 52 and 53, respectively; and
c) an anti-human epidermal growth factor receptor 3 (HER3) antibody comprising a heavy chain and a light chain that comprise the amino acid sequences of:
SEQ ID NOs: 54 and 55, respectively,
SEQ ID NOs: 56 and 57, respectively,
SEQ ID NOs: 58 and 59, respectively, or
SEQ ID NOs: 60 and 61, respectively.
19. The method of claim 18 , wherein said antibody composition comprises:
a) an anti-epidermal growth factor receptor (EGFR) antibody comprising the heavy chain variable region (VH) amino acid sequence of SEQ ID NO: 42 and the light chain variable region (VL) amino acid sequence of SEQ ID NO: 43;
b) an anti-EGFR antibody comprising the VH amino acid sequence of SEQ ID NO: 46 and the VL amino acid sequence of SEQ ID NO: 47;
c) an anti-human epidermal growth factor receptor 2 (HER2) antibody comprising the VH amino acid sequence of SEQ ID NO: 50 and the VL amino acid sequence of SEQ ID NO: 51;
d) an anti-HER2 antibody comprising the VH amino acid sequence of SEQ ID NO: 52 and the VL amino acid sequence of SEQ ID NO: 53;
e) an anti-human epidermal growth factor receptor 3 (HER3) antibody comprising the VH amino acid sequence of SEQ ID NO: 54 and the VL amino acid sequence of SEQ ID NO: 55; and
f) an anti-HER3 antibody comprising the VH amino acid sequence of SEQ ID NO: 60 and the VL amino acid sequence of SEQ ID NO: 61.
20. The method of claim 18 , wherein said antibody composition has at least one of the following properties:
a) reduces EGFR, HER2, or HER3 expression in cancer cells in the patient; and
b) prevents EGFR, HER2, or HER3 up-regulation in cancer cells in the patient.