ANTI-CEA ANTIBODIES AND METHODS OF USE
The present disclosure provides for antibodies and antigen-binding fragments thereof that bind to human CEA, a pharmaceutical composition comprising said antibody, and use of the anti-CEA antibody or the composition for treating a disease, such as cancer.
1 . An anti-CEA antibody or antigen-binding fragment thereof, comprising an antibody or antigen-binding fragment thereof that specifically binds to human CEA at amino acids 596 to 674 of SEQ ID NO:52.
2 . The anti-CEA antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof does not bind to other CEACAM family members.
3 . The anti-CEA antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises:
(i) a heavy chain variable region that comprises (a) a HCDR1 of SEQ ID NO: 7, (b) a HCDR2 of SEQ ID NO:8, and (c) a HCDR3 of SEQ ID NO:9; and a light chain variable region that comprises: (d) a LCDR1 of SEQ ID NO: 10, (e) a LCDR2 of SEQ ID NO: 11, and (f) a LCDR3 of SEQ ID NO:6;
(ii) a heavy chain variable region that comprises (a) a HCDR1 of SEQ ID NO:24, (b) a HCDR2 of SEQ ID NO:25, and (c) a HCDR3 of SEQ ID NO:26; and a light chain variable region that comprises: (d) a LCDR1 of SEQ ID NO:27, (e) a LCDR2 of SEQ ID NO:28, and (f) a LCDR3 of SEQ ID NO: 23; or
(iii) a heavy chain variable region that comprises (a) a HCDR1 of SEQ ID NO:41, (b) a HCDR2 of SEQ ID NO:42, and (c) a HCDR3 of SEQ ID NO:43; and a light chain variable region that comprises: (d) a LCDR1 of SEQ ID NO:44, (e) a LCDR2 of SEQ ID NO:45, and (f) a LCDR3 of SEQ ID NO:40.
4 . The anti-CEA antibody or antigen-binding fragment thereof of claim 3 , wherein the antibody or antigen-binding fragment thereof comprises:
(i) a heavy chain variable region comprising an amino acid sequence at least 90% identical to SEQ ID NO: 14, and a light chain variable region comprising an amino acid sequence at least 90% identical to SEQ ID NO: 15;
(ii) a heavy chain variable region comprising an amino acid sequence at least 90% identical to SEQ ID NO: 31, and a light chain variable region comprising an amino acid sequence at least 90% identical to SEQ ID NO: 32; or
(iii) a heavy chain variable region comprising an amino acid sequence at least 90% identical to SEQ ID NO: 48, and a light chain variable region comprising an amino acid sequence at least 90% identical to SEQ ID NO: 49.
5 . The anti-CEA antibody or antigen-binding fragment thereof of claim 4 , wherein one, two, three, four, five, six, seven, eight, nine, or ten amino acids within SEQ ID NO:14, 15, 31, 32, 48, or 49 have been inserted, deleted or substituted.
6 . The anti-CEA antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises:
(i) a heavy chain variable region that comprises SEQ ID NO:14, and a light chain variable region (VL) that comprises SEQ ID NO: 15;
(ii) a heavy chain variable region that comprises SEQ ID NO: 31, and a light chain variable region (VL) that comprises SEQ ID NO: 32; or
(iii) a heavy chain variable region that comprises SEQ ID NO: 48, and a light chain variable region (VL) that comprises SEQ ID NO: 49.
7 . The anti-CEA antibody or antigen-binding fragment thereof of claim 1 , wherein the anti-CEA antibody or antigen-binding fragment thereof is a monoclonal antibody, a chimeric antibody, a humanized antibody, a human engineered antibody, a single chain antibody (scFv), a Fab fragment, a Fab′ fragment, or a F(ab′)2 fragment.
8 . The anti-CEA antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof has one or more of antibody dependent cellular cytotoxicity (ADCC) or complement dependent cytotoxicity (CDC).
9 . The anti-CEA antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof has reduced glycosylation or no glycosylation or is hypofucosylated.
10 . The anti-CEA antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof comprises increased bisecting GlcNac structures.
11 . The anti-CEA antibody or antigen-binding fragment thereof of claim 1 , wherein the Fc domain is an IgG1.
12 . The anti-CEA antibody or antigen-binding fragment thereof of claim 1 , wherein the antibody or antigen-binding fragment thereof is conjugated to a toxin.
13 . A pharmaceutical composition comprising the anti-CEA antibody or antigen-binding fragment thereof of claim 1 , and a pharmaceutically acceptable carrier.
14 . A method of treating cancer comprising administering to a patient in need an effective amount of the antibody or antigen-binding fragment thereof of claim 1 .
15 . The method of claim 14 , wherein the cancer is gastric cancer, colon cancer, pancreatic cancer, breast cancer, head and neck cancer, kidney cancer, liver cancer, small cell lung cancer, non-small cell lung cancer, ovarian cancer, skin cancer, mesothelioma, lymphoma, leukemia, myeloma, or sarcoma.
16 . The method of claim 14 , wherein the antibody or antigen-binding fragment thereof is administered in combination with another therapeutic agent, wherein the therapeutic agent is an anti-PD1 or anti-PDL1 antibody, paclitaxel or a paclitaxel agent, docetaxel, carboplatin, topotecan, cisplatin, irinotecan, doxorubicin, lenalidomide, or 5-azacytidine.
17 .- 18 . (canceled)
19 . An isolated nucleic acid that encodes the anti-CEA antibody or antigen-binding fragment thereof of claim 1 .
20 . A vector comprising the nucleic acid of claim 19 .
21 . A host cell comprising the nucleic acid of claim 19 .
22 . A process for producing an anti-CEA antibody or antigen-binding fragment thereof comprising cultivating the host cell of claim 21 and recovering the antibody or antigen-binding fragment thereof from the culture.