Anti-ceacam5 antibodies and uses thereof

An isolated antibody or antigen binding fragment thereof which competes for binding to A3-B3 domain of human and Macaca fascicularis CEACAM5 proteins with an antibody comprising the variable heavy and light chains of an antibody selected from the group consisting of

• a) an antibody comprising a heavy chain variable domain having an amino acid sequence of SEQ ID NO:31 and a light chain variable domain having an amino acid sequence of SEQ ID NO:32;
• b) an antibody comprising a heavy chain variable domain having an amino acid sequence of SEQ ID NO:33 and a light chain variable domain having an amino acid sequence of SEQ ID NO:34;
• c) an antibody comprising a heavy chain variable domain having an amino acid sequence of SEQ ID NO:33 and a light chain variable domain having an amino acid sequence of SEQ ID NO:34 in which K at position 52 has been replaced by R;
• d) an antibody comprising a heavy chain variable domain having an amino acid sequence of SEQ ID NO:35 and a light chain variable domain having an amino acid sequence of SEQ ID NO:36;
• e) an antibody comprising a heavy chain variable domain having an amino acid sequence of SEQ ID NO:37 and a light chain variable domain having an amino acid sequence of SEQ ID NO:38;
• and
• f) an antibody comprising a heavy chain variable domain having an amino acid sequence of SEQ ID NO:39 and a light chain variable domain having an amino acid sequence of SEQ ID NO:40.

An isolated antibody or antigen binding fragment thereof which binds to A3-B3 domain of human and Macaca fascicularis CEACAM5 proteins and which comprises:

• a) a CDR1-H comprising an amino acid sequence of SEQ ID NO:1 or a sequence differing from SEQ ID NO:1 by one amino acid substitution;
• a CDR2-H comprising an amino acid sequence of SEQ ID NO:2 or a sequence differing from SEQ ID NO:2 by one or more amino acid substitutions;
• a CDR3-H comprising an amino acid sequence of SEQ ID NO:3 or a sequence differing from SEQ ID NO:3 by one amino acid substitution;
• a CDR1-L comprising an amino acid sequence of SEQ ID NO:4 or a sequence differing from SEQ ID NO:4 by one amino acid substitution;
• a CDR2-L comprising an amino acid sequence of SAS or a sequence differing from SAS by one amino acid substitution;
• and a CDR3-L comprising an amino acid sequence of SEQ ID NO:6 or a sequence differing from SEQ ID NO:6 by one amino acid substitution;
• or
• b) a CDR1-H comprising an amino acid sequence of SEQ ID NO:7 or a sequence differing from SEQ ID NO:7 by one amino acid substitution;
• a CDR2-H comprising an amino acid sequence of SEQ ID NO:8 or a sequence differing from SEQ ID NO:8 by one or more amino acid substitutions;
• a CDR3-H comprising an amino acid sequence of SEQ ID NO:9 or a sequence differing from SEQ ID NO:9 by one amino or more acid substitutions;
• a CDR1-L comprising an amino acid sequence of SEQ ID NO:10 or a sequence differing from SEQ ID NO:10 by one amino acid substitution;
• a CDR2-L comprising an amino acid sequence of NTK or NTR or a sequence differing from NTK or NTR by one amino acid substitution, and a CDR3-L comprising an amino acid sequence of SEQ ID NO:12 or a sequence differing from SEQ ID NO:12 by one amino acid substitution;
• or
• c) a CDR1-H comprising an amino acid sequence of SEQ ID NO:13 or a sequence differing from SEQ ID NO:13 by one amino acid substitution;
• a CDR2-H comprising an amino acid sequence of SEQ ID NO:14 or a sequence differing from SEQ ID NO:14 by one or more amino acid substitutions;
• a CDR3-H comprising an amino acid sequence of SEQ ID NO:15 or a sequence differing from SEQ ID NO:15 by one amino acid substitution;
• a CDR1-L comprising an amino acid sequence of SEQ ID NO:16 or a sequence differing from SEQ ID NO:16 by one amino acid substitution;
• a CDR2-L comprising an amino acid sequence of SAS or a sequence differing from SAS by one amino acid substitution;
• and a CDR3-L comprising an amino acid sequence of SEQ ID NO:18 or a sequence differing from SEQ ID NO:18 by one amino acid substitution;
• or
• d) a CDR1-H comprising an amino acid sequence of SEQ ID NO:19 or a sequence differing from SEQ ID NO:19 by one amino acid substitution;
• a CDR2-H comprising an amino acid sequence of SEQ ID NO:20 or a sequence differing from SEQ ID NO:20 by one or more amino acid substitutions;
• a CDR3-H comprising an amino acid sequence of SEQ ID NO:21 or a sequence differing from SEQ ID NO:21 by one or more amino acid substitutions;
• a CDR1-L comprising an amino acid sequence of SEQ ID NO:22 or a sequence differing from SEQ ID NO:22 by one amino acid substitution;
• a CDR2-L comprising an amino acid sequence of NAK or a sequence differing from NAK by one or more amino acid substitutions and a CDR3-L comprising an amino acid sequence of SEQ ID NO:24 or a sequence differing from SEQ ID NO:24 by one amino acid substitution;
• or
• e) a CDR1-H comprising an amino acid sequence of SEQ ID NO:25 or a sequence differing from SEQ ID NO:25 by one amino acid substitution;
• a CDR2-H comprising an amino acid sequence of SEQ ID NO:26 or a sequence differing from SEQ ID NO:26 by one or more amino acid substitutions;
• a CDR3-H comprising an amino acid sequence of SEQ ID NO:27 or a sequence differing from SEQ ID NO:27 by one or more amino acid substitutions;
• a CDR1-L comprising an amino acid sequence of SEQ ID NO:28 or a sequence differing from SEQ ID NO:28 by one amino acid substitution;
• a CDR2-L comprising an amino acid sequence of NAK or a sequence differing from NAK by one or more amino acid substitutions and a CDR3-L comprising an amino acid sequence of SEQ ID NO:30 or a sequence differing from SEQ ID NO:30 by one amino acid substitution.

An isolated nucleic acid comprising a sequence encoding an antibody or antigen binding fragment thereof wherein said antibody or antigen binding fragment thereof comprises

• a) a CDR1-H comprising an amino acid sequence of SEQ ID NO:1 or an amino acid a sequence differing from SEQ ID NO:1 by one amino acid substitution;
• a CDR2-H comprising an amino acid sequence of SEQ ID NO:2 or an amino acid sequence differing from SEQ ID NO:2 by one or more amino acid substitutions;
• a CDR3-H comprising an amino acid sequence of SEQ ID NO:3 or an amino acid sequence differing from SEQ ID NO:3 by one amino acid substitution;
• a CDR1-L comprising an amino acid sequence of SEQ ID NO:4 or an amino acid sequence differing from SEQ ID NO:4 by one amino acid substitution;
• a CDR2-L comprising an amino acid sequence of SAS or an amino acid sequence differing from SAS by one amino acid substitution;
• and a CDR3-L comprising an amino acid sequence of SEQ ID NO:6 or an amino acid sequence differing from SEQ ID NO:6 by one amino acid substitution;
• or
• b) a CDR1-H comprising an amino acid sequence of SEQ ID NO:7 or a sequence differing from SEQ ID NO:7 by one amino acid substitution;
• a CDR2-H comprising an amino acid sequence of SEQ ID NO:8 or a sequence differing from SEQ ID NO:8 by one or more amino acid substitutions;
• a CDR3-H comprising an amino acid sequence of SEQ ID NO:9 or a sequence differing from SEQ ID NO:9 by one or more amino acid substitutions;
• a CDR1-L comprising an amino acid sequence of SEQ ID NO:10 or a sequence differing from SEQ ID NO:10 by one amino acid substitution;
• a CDR2-L comprising an amino acid sequence of NTK or NTR or a sequence differing from NTK or NTR by one amino acid substitution;
• and a CDR3-L comprising an amino acid sequence of SEQ ID NO:12 or a sequence differing from SEQ ID NO:12 by one amino acid substitution;
• or
• c) a CDR1-H comprising an amino acid sequence of SEQ ID NO:13 or a sequence differing from SEQ ID NO:13 by one amino acid substitution;
• a CDR2-H comprising an amino acid sequence of SEQ ID NO:14 or a sequence differing from SEQ ID NO:14 by one or more amino acid substitutions;
• a CDR3-H comprising an amino acid sequence of SEQ ID NO:15 or a sequence differing from SEQ ID NO:15 by one amino acid substitution;
• a CDR1-L comprising an amino acid sequence of SEQ ID NO:16 or a sequence differing from SEQ ID NO:16 by one amino acid substitution;
• a CDR2-L comprising an amino acid SAS or a sequence differing from SAS by one amino acid substitution;
• and a CDR3-L comprising an amino acid sequence of SEQ ID NO:18 or a sequence differing from SEQ ID NO:18 by one amino acid substitution;
• or
• d) a CDR1-H comprising an amino acid sequence of SEQ ID NO:19 or a sequence differing from SEQ ID NO:19 by one amino acid substitution;
• a CDR2-H comprising an amino acid sequence of SEQ ID NO:20 or a sequence differing from SEQ ID NO:20 by one or more amino acid substitutions;
• a CDR3-H comprising an amino acid sequence of SEQ ID NO:21 or a sequence differing from SEQ ID NO:21 by one or more amino acid substitutions;
• a CDR1-L comprising an amino acid sequence of SEQ ID NO:22 or a sequence differing from SEQ ID NO:22 by one amino acid substitution;
• a CDR2-L comprising an amino acid sequence of NAK or a sequence differing from NAK by one or more amino acid substitutions;
• and a CDR3-L comprising an amino acid sequence of SEQ ID NO:24 or a sequence differing from SEQ ID NO:24 by one amino acid substitution;
• or
• e) a CDR1-H comprising an amino acid sequence of SEQ ID NO:25 or a sequence differing from SEQ ID NO:25 by one amino acid substitution;
• a CDR2-H comprising an amino acid sequence of SEQ ID NO:26 or a sequence differing from SEQ ID NO:26 by one or more amino acid substitutions;
• a CDR3-H comprising an amino acid sequence of SEQ ID NO:27 or a sequence differing from SEQ ID NO:27 by one or more amino acid substitutions;
• a CDR1-L comprising an amino acid sequence of SEQ ID NO:28 or a sequence differing from SEQ ID NO:28 by one amino acid substitution;
• a CDR2-L of sequence NAK or a sequence differing from NAK by one or more amino acid substitutions;
• and a CDR3-L comprising an amino acid sequence of SEQ ID NO:30 or a sequence differing from SEQ ID NO:30 by one amino acid substitution.

A method of treating a patient comprising administering to the patient an antibody or antigen binding fragment thereof which binds to A3-B3 domain of human and Macaca fascicularis CEACAM5 proteins, wherein the patient has a CEACAM5 expressing cancer and wherein the antibody or antigen binding fragment thereof comprises:

• a) a CDR1-H comprising an amino acid sequence of SEQ ID NO:1 or an amino acid sequence differing from SEQ ID NO:1 by one amino acid substitution;
• a CDR2-H comprising an amino acid sequence of SEQ ID NO:2 or an amino acid sequence differing from SEQ ID NO:2 by one or more amino acid substitutions;
• a CDR3-H comprising an amino acid sequence of SEQ ID NO:3 or an amino acid sequence differing from SEQ ID NO:3 by one amino acid substitution;
• a CDR1-L comprising an amino acid sequence of SEQ ID NO:4 or an amino acid sequence differing from SEQ ID NO:4 by one amino acid substitution;
• a CDR2-L comprising an amino acid sequence of SAS or an amino acid sequence differing from SAS by one amino acid substitution;
• and a CDR3-L comprising an amino acid sequence of SEQ ID NO:6 or an amino acid sequence differing from SEQ ID NO:6 by one amino acid substitution;
• or
• b) a CDR1-H comprising an amino acid sequence of SEQ ID NO:7 or a sequence differing from SEQ ID NO:7 by one amino acid substitution;
• a CDR2-H comprising an amino acid sequence of SEQ ID NO:8 or a sequence differing from SEQ ID NO:8 by one or more amino acid substitutions;
• a CDR3-H comprising an amino acid sequence of SEQ ID NO:9 or a sequence differing from SEQ ID NO:9 by one or more amino acid substitutions;
• a CDR1-L comprising an amino acid sequence of SEQ ID NO:10 or a sequence differing from SEQ ID NO:10 by one amino acid substitution;
• a CDR2-L comprising an amino acid sequence of NTK or NTR or a sequence differing from NTK or NTR by one amino acid substitution;
• and a CDR3-L comprising an amino acid sequence of SEQ ID NO:12 or a sequence differing from SEQ ID NO:12 by one amino acid substitution;
• or
• c) a CDR1-H comprising an amino acid sequence of SEQ ID NO:13 or a sequence differing from SEQ ID NO:13 by one amino acid substitution;
• a CDR2-H comprising an amino acid sequence of SEQ ID NO:14 or a sequence differing from SEQ ID NO:14 by one or more amino acid substitutions;
• a CDR3-H comprising an amino acid sequence of SEQ ID NO:15 or a sequence differing from SEQ ID NO:15 by one amino acid substitution;
• a CDR1-L comprising an amino acid sequence of SEQ ID NO:16 or a sequence differing from SEQ ID NO:16 by one amino acid substitution;
• a CDR2-L comprising an amino acid sequence of SAS or a sequence differing from SAS by one amino acid substitution;
• and a CDR3-L comprising an amino acid sequence of SEQ ID NO:18 or a sequence differing from SEQ ID NO:18 by one amino acid substitution;
• or
• d) a CDR1-H comprising an amino acid sequence of SEQ ID NO:19 or a sequence differing from SEQ ID NO:19 by one amino acid substitution;
• a CDR2-H comprising an amino acid sequence of SEQ ID NO:20 or a sequence differing from SEQ ID NO:20 by one or more amino acid substitutions;
• a CDR3-H comprising an amino acid sequence of SEQ ID NO:21 or a sequence differing from SEQ ID NO:21 by one or more amino acid substitutions;
• a CDR1-L comprising an amino acid sequence of SEQ ID NO:22 or a sequence differing from SEQ ID NO:22 by one amino acid substitution;
• a CDR2-L comprising an amino acid sequence of NAK or a sequence differing from NAK by one or more amino acid substitutions;
• and a CDR3-L comprising an amino acid sequence of SEQ ID NO:24 or a sequence differing from SEQ ID NO:24 by one amino acid substitution;
• or
• e) a CDR1-H comprising an amino acid sequence of SEQ ID NO:25 or a sequence differing from SEQ ID NO:25 by one amino acid substitution;
• a CDR2-H comprising an amino acid sequence of SEQ ID NO:26 or a sequence differing from SEQ ID NO:26 by one or more amino acid substitutions;
• a CDR3-H comprising an amino acid sequence of SEQ ID NO:27 or a sequence differing from SEQ ID NO:27 by one or more amino acid substitutions;
• a CDR1-L comprising an amino acid sequence of SEQ ID NO:28 or a sequence differing from SEQ ID NO:28 by one amino acid substitution;
• a CDR2-L of sequence NAK or a sequence differing from NAK by one or more amino acid substitutions;
• and a CDR3-L comprising an amino acid sequence of SEQ ID NO:30 or a sequence differing from SEQ ID NO:30 by one amino acid substitution.

A method of treating a patient comprising administering an immunoconjugate comprising an antibody or antigen binding fragment thereof linked to at least one growth inhibitory agent to the patient, wherein the patient has a CEACAM5 expressing cancer, wherein the antibody or antigen binding fragment thereof binds to A3-B3 domain of human and Macaca fascicularis CEACAM5 proteins and comprises:

• a) a CDR1-H comprising an amino acid sequence of SEQ ID NO:1 or an amino acid sequence differing from SEQ ID NO:1 by one amino acid substitution;
• a CDR2-H comprising an amino acid sequence of SEQ ID NO:2 or an amino acid sequence differing from SEQ ID NO:2 by one or more amino acid substitutions;
• a CDR3-H comprising an amino acid sequence of SEQ ID NO:3 or an amino acid sequence differing from SEQ ID NO:3 by one amino acid substitution;
• a CDR1-L comprising an amino acid sequence of SEQ ID NO:4 or an amino acid sequence differing from SEQ ID NO:4 by one amino acid substitution;
• a CDR2-L comprising an amino acid sequence of SAS or an amino acid sequence differing from SAS by one amino acid substitution;
• and a CDR3-L comprising an amino acid sequence of SEQ ID NO:6 or an amino acid sequence differing from SEQ ID NO:6 by one amino acid substitution;
• or
• b) a CDR1-H comprising an amino acid sequence of SEQ ID NO:7 or a sequence differing from SEQ ID NO:7 by one amino acid substitution;
• a CDR2-H comprising an amino acid sequence of SEQ ID NO:8 or a sequence differing from SEQ ID NO:8 by one or more amino acid substitutions;
• a CDR3-H comprising an amino acid sequence of SEQ ID NO:9 or a sequence differing from SEQ ID NO:9 by one or more amino acid substitutions;
• a CDR1-L comprising an amino acid sequence of SEQ ID NO:10 or a sequence differing from SEQ ID NO:10 by one amino acid substitution;
• a CDR2-L comprising an amino acid sequence of NTK or NTR or a sequence differing from NTK or NTR by one amino acid substitution;
• and a CDR3-L comprising an amino acid sequence of SEQ ID NO:12 or a sequence differing from SEQ ID NO:12 by one amino acid substitution;
• or
• c) a CDR1-H comprising an amino acid sequence of SEQ ID NO:13 or a sequence differing from SEQ ID NO:13 by one amino acid substitution;
• a CDR2-H comprising an amino acid sequence of SEQ ID NO:14 or a sequence differing from SEQ ID NO:14 by one or more amino acid substitutions;
• a CDR3-H comprising an amino acid sequence of SEQ ID NO:15 or a sequence differing from SEQ ID NO:15 by one amino acid substitution;
• a CDR1-L comprising an amino acid sequence of SEQ ID NO:16 or a sequence differing from SEQ ID NO:16 by one amino acid substitution;
• a CDR2-L comprising an amino acid sequence of SAS or a sequence differing from SAS by one amino acid substitution;
• and a CDR3-L comprising an amino acid sequence of SEQ ID NO:18 or a sequence differing from SEQ ID NO:18 by one amino acid substitution;
• or
• d) a CDR1-H comprising an amino acid sequence of SEQ ID NO:19 or a sequence differing from SEQ ID NO:19 by one amino acid substitution;
• a CDR2-H comprising an amino acid sequence of SEQ ID NO:20 or a sequence differing from SEQ ID NO:20 by one or more amino acid substitutions;
• a CDR3-H comprising an amino acid sequence of SEQ ID NO:21 or a sequence differing from SEQ ID NO:21 by one or more amino acid substitutions;
• a CDR1-L comprising an amino acid sequence of SEQ ID NO:22 or a sequence differing from SEQ ID NO:22 by one amino acid substitution;
• a CDR2-L comprising an amino acid sequence of NAK or a sequence differing from NAK by one or more amino acid substitutions;
• and a CDR3-L comprising an amino acid sequence of SEQ ID NO:24 or a sequence differing from SEQ ID NO:24 by one amino acid substitution;
• or
• e) a CDR1-H comprising an amino acid sequence of SEQ ID NO:25 or a sequence differing from SEQ ID NO:25 by one amino acid substitution;
• a CDR2-H comprising an amino acid sequence of SEQ ID NO:26 or a sequence differing from SEQ ID NO:26 by one or more amino acid substitutions;
• a CDR3-H comprising an amino acid sequence of SEQ ID NO:27 or a sequence differing from SEQ ID NO:27 by one or more amino acid substitutions;
• a CDR1-L comprising an amino acid sequence of SEQ ID NO:28 or a sequence differing from SEQ ID NO:28 by one amino acid substitution;
• a CDR2-L of sequence NAK or a sequence differing from NAK by one or more amino acid substitutions;
• and a CDR3-L comprising an amino acid sequence of SEQ ID NO:30 or a sequence differing from SEQ ID NO:30 by one amino acid substitution.

A method of detecting cancer in a patient comprising,

• a) contacting a biological sample from the patient with an antibody or antigen binding fragment thereof which binds to A3-B3 domain of human and Macaca fascicularis CEACAM5 proteins, wherein the patient has a CEACAM5 expressing cancer and wherein the antibody or antigen binding fragment thereof comprises:
• i) a CDR1-H comprising an amino acid sequence of SEQ ID NO:1 or an amino acid sequence differing from SEQ ID NO:1 by one amino acid substitution;
• a CDR2-H comprising an amino acid sequence of SEQ ID NO:2 or an amino acid sequence differing from SEQ ID NO:2 by one or more amino acid substitutions;
• a CDR3-H comprising an amino acid sequence of SEQ ID NO:3 or an amino acid sequence differing from SEQ ID NO:3 by one amino acid substitution;
• a CDR1-L comprising an amino acid sequence of SEQ ID NO:4 or an amino acid sequence differing from SEQ ID NO:4 by one amino acid substitution;
• a CDR2-L comprising an amino acid sequence of SAS or an amino acid sequence differing from SAS by one amino acid substitution;
• and a CDR3-L comprising an amino acid sequence of SEQ ID NO:6 or an amino acid sequence differing from SEQ ID NO:6 by one amino acid substitution;
• or
• ii) a CDR1-H comprising an amino acid sequence of SEQ ID NO:7 or a sequence differing from SEQ ID NO:7 by one amino acid substitution;
• a CDR2-H comprising an amino acid sequence of SEQ ID NO:8 or a sequence differing from SEQ ID NO:8 by one or more amino acid substitutions;
• a CDR3-H comprising an amino acid sequence of SEQ ID NO:9 or a sequence differing from SEQ ID NO:9 by one or more amino acid substitutions;
• a CDR1-L comprising an amino acid sequence of SEQ ID NO:10 or a sequence differing from SEQ ID NO:10 by one amino acid substitution;
• a CDR2-L comprising an amino acid sequence of NTK or NTR or a sequence differing from NTK or NTR by one amino acid substitution;
• and a CDR3-L comprising an amino acid sequence of SEQ ID NO:12 or a sequence differing from SEQ ID NO:12 by one amino acid substitution;
• or
• iii) a CDR1-H comprising an amino acid sequence of SEQ ID NO:13 or a sequence differing from SEQ ID NO:13 by one amino acid substitution;
• a CDR2-H comprising an amino acid sequence of SEQ ID NO:14 or a sequence differing from SEQ ID NO:14 by one or more amino acid substitutions;
• a CDR3-H comprising an amino acid sequence of SEQ ID NO:15 or a sequence differing from SEQ ID NO:15 by one amino acid substitution;
• a CDR1-L comprising an amino acid sequence of SEQ ID NO:16 or a sequence differing from SEQ ID NO:16 by one amino acid substitution;
• a CDR2-L comprising an amino acid sequence of SAS or a sequence differing from SAS by one amino acid substitution;
• and a CDR3-L comprising an amino acid sequence of SEQ ID NO:18 or a sequence differing from SEQ ID NO:18 by one amino acid substitution;
• or
• iv) a CDR1-H comprising an amino acid sequence of SEQ ID NO:19 or a sequence differing from SEQ ID NO:19 by one amino acid substitution;
• a CDR2-H comprising an amino acid sequence of SEQ ID NO:20 or a sequence differing from SEQ ID NO:20 by one or more amino acid substitutions;
• a CDR3-H comprising an amino acid sequence of SEQ ID NO:21 or a sequence differing from SEQ ID NO:21 by one or more amino acid substitutions;
• a CDR1-L comprising an amino acid sequence of SEQ ID NO:22 or a sequence differing from SEQ ID NO:22 by one amino acid substitution;
• a CDR2-L comprising an amino acid sequence of NAK or a sequence differing from NAK by one or more amino acid substitutions;
• and a CDR3-L comprising an amino acid sequence of SEQ ID NO:24 or a sequence differing from SEQ ID NO:24 by one amino acid substitution;
• or
• v) a CDR1-H comprising an amino acid sequence of SEQ ID NO:25 or a sequence differing from SEQ ID NO:25 by one amino acid substitution;
• a CDR2-H comprising an amino acid sequence of SEQ ID NO:26 or a sequence differing from SEQ ID NO:26 by one or more amino acid substitutions;
• a CDR3-H comprising an amino acid sequence of SEQ ID NO:27 or a sequence differing from SEQ ID NO:27 by one or more amino acid substitutions;
• a CDR1-L comprising an amino acid sequence of SEQ ID NO:28 or a sequence differing from SEQ ID NO:28 by one amino acid substitution;
• a CDR2-L of sequence NAK or a sequence differing from NAK by one or more amino acid substitutions;
• and a CDR3-L comprising an amino acid sequence of SEQ ID NO:30 or a sequence differing from SEQ ID NO:30 by one amino acid substitution;
• (b) measuring bound antibody or antigen binding fragment thereof to said biological sample;
• and
• (c) detecting the cancer by comparing the bound antibody or antigen fragment thereof with a control, wherein an increased level of bound antibody or antigen binding fragment thereof compared to control being indicative of a cancer.