Neutralizing anti-CCL20 antibodies
The present invention relates to novel humanized, chimeric and murine antibodies that have binding specificity for the human CC chemokine ligand 20 (CCL20). The present invention further relates to heavy chains and light chains of said antibodies. The invention also relates to isolated nucleic acids, recombinant vectors and host cells that comprise a sequence which encodes a heavy chain and/or a light chain of said antibodies, and to a method of preparing said antibodies. The anti-CCL20 antibodies of the invention can be used in therapeutic applications to treat, for example, inflammatory and autoimmune disorders and cancer.
1. A monoclonal anti-human CCL20 antibody or an antigen-binding portion thereof, whose heavy chain complementarity determining region 1 (CDR1), complementarity determining region 2 (CDR2), and complementarity determining region 3 (CDR3) and whose light chain CDR1, CDR2, and CDR3 comprise the amino acid sequences of:
a) SEQ ID NOS: 60, 64, 67, 70, 73, and 75, respectively;
b) SEQ ID NOS: 60, 64, 67, 71, 73, and 75, respectively;
c) SEQ ID NOS: 77, 79, 67, 70, 73, and 75, respectively; or
d) SEQ ID NOS: 77, 79, 67, 71, 73, and 75, respectively;
wherein said monoclonal antibody or antigen-binding portion further comprises a detectable label.
2. The antibody or antigen-binding portion of claim 1 , wherein the heavy chain variable domain of the antibody comprises the amino acid sequence of SEQ ID NO: 9.
3. The antibody or antigen-binding portion of claim 2 , wherein the light chain variable domain of the antibody comprises the amino acid sequence shown in SEQ ID NO: 15 or SEQ ID NO: 16.
4. The antibody or antigen-binding portion of claim 1 , wherein:
the heavy chain of the antibody comprises the amino acid sequence of SEQ ID NO: 108, or the amino acid sequence of SEQ ID NO: 108 without the C-terminal lysine; or
the light chain of the antibody comprises the amino acid sequence of SEQ ID NO: 110 or 112.
5. The antibody or antigen-binding portion of claim 4 , wherein said heavy chain and said light chain comprise amino acid sequences selected from the group consisting of:
a) SEQ ID NO: 1 and SEQ ID NO: 7, respectively;
b) SEQ ID NO: 1 and SEQ ID NO: 8, respectively;
c) SEQ ID NO: 108 and SEQ ID NO: 110, respectively;
d) SEQ ID NO: 108 and SEQ ID NO: 112, respectively;
e) SEQ ID NO: 108 without the C-terminal lysine and SEQ ID NO: 110, respectively; and
f) SEQ ID NO: 108 without the C-terminal lysine and SEQ ID NO: 112, respectively.
6. A monoclonal antibody whose heavy chain and light chain comprise the amino acid sequences of SEQ ID NO: 108 and SEQ ID NO: 110, respectively, wherein said monoclonal antibody further comprises a detectable label.
7. The antibody or antigen-binding portion of any one of claims 2 , 5 , and 6 , wherein said detectable label is selected from the group consisting of: a radioisotope, a positron emitting label, a paramagnetic ion, an epitope label, an affinity label, a spin label, an enzyme, a fluorescent group, and a chemiluminescent group.