Polypeptides and antibodies derived from chronic lymphocytic leukemia cells and uses thereof
Cancer treatments use a therapy that: 1) interferes with the interaction between CD200 and its receptor to block immune suppression thereby promoting eradication of the cancer cells; and 2) directly kills the cancer cells either by complement-mediated or antibody-dependent cellular cytotoxicity or by targeting cells using a fusion molecule that includes a CD200-targeting portion. The therapy includes the administration of novel antibodies, functional fragments thereof or fusion molecules containing portions thereof.
1. An anti-CD200 antibody or antigen-binding fragment thereof that binds to CD200, wherein the antibody or antigen-binding fragment comprises:
a light chain CDR3 having the sequence set forth in residues 91-99 of SEQ ID NO: 209; a light chain CDR2 having the sequence set forth in residues 52-58 of SEQ ID NO: 209; a light chain CDR1 having the sequence set forth in residues 26-36 of SEQ ID NO: 209; a heavy chain CDR3 having the sequence set forth in SEQ ID NO: 195; a heavy chain CDR2 having the sequence set forth in SEQ ID NO: 174; and a heavy chain CDR1 having the sequence set forth in SEQ ID NO: 149.
2. The antibody or antigen-binding fragment of claim 1 , wherein the antibody or antigen-binding fragment comprises a heavy chain variable region having the sequence set forth in SEQ ID NO: 203.
3. The antibody or antigen-binding fragment of claim 1 , wherein the antibody or antigen-binding fragment comprises a light chain variable region having the sequence set forth in SEQ ID NO: 209.
4. The antibody or antigen-binding fragment of claim 1 , wherein the antibody or antigen-binding fragment comprises a heavy chain variable region having the sequence set forth in SEQ ID NO: 203 and a light chain variable region having the sequence set forth in SEQ ID NO: 209.
5. The antibody or antigen-binding fragment of claim 1 , wherein the antibody is selected from the group consisting of a monoclonal antibody, a humanized antibody, and a chimeric antibody.
6. The antigen-binding fragment of claim 1 , wherein the antigen-binding fragment is selected from the group consisting of an Fv, scFv, Fab′ and F(a b′) 2 .
7. The antigen-binding fragment of claim 6 , wherein the antigen-binding fragment is a humanized antigen-binding fragment.
8. A fusion molecule comprising:
a first portion that targets cells bearing the OX-2/CD200 antigen, wherein the first portion is an anti-CD200 antibody or antigen binding fragment thereof that binds to CD200 comprising (i) a light chain CDR1 having the sequence set forth in residues 26-36 of SEQ ID NO: 209, (ii) a light chain CDR2 having the sequence set forth in residues 52-58 of SEQ ID NO: 209, (iii) a light chain CDR3 having the sequence set forth in residues 91-99 of SEQ ID NO: 209, (iv) a heavy chain CDR1 having the sequence set forth in SEQ ID NO: 149, (v) a heavy chain CDR2 having the sequence set forth in SEQ ID NO: 174, and (vi) a heavy chain CDR3 having the sequence set forth in SEQ ID NO: 195; and
a second portion that promotes the death of cells, wherein the second portion is a cytotoxic compound selected from the group consisting of a cytotoxic drug, a bacterial toxin, a radioactive isotope, an immunoglobulin constant region having antibody-dependent cellular cytotoxicity (ADCC) activity, and an immunoglobulin constant region having complement dependent cytotoxicity (CDC) activity.
9. A composition comprising an antibody or antigen-binding fragment thereof of claim 1 and a pharmaceutically acceptable carrier.
10. The fusion molecule of claim 8 , wherein said first portion is an antigen binding fragment of an anti-CD200 monoclonal antibody.
11. The fusion molecule of claim 8 , wherein the anti-CD200 antibody is a humanized antibody, or an antigen binding fragment thereof.
12. The fusion molecule of claim 8 , wherein the antigen-binding fragment is selected from the group consisting of an Fv, scFv, Fab′ or F(ab′) 2 .
13. A composition comprising a fusion molecule of claim 8 and a pharmaceutically acceptable carrier.
14. The fusion molecule of claim 8 , wherein the antibody or antigen-binding fragment comprises a heavy chain variable region having the sequence set forth in SEQ ID NO: 203.
15. The fusion molecule of claim 8 , wherein the antibody or antigen-binding fragment comprises a light chain variable region having the sequence set forth in SEQ ID NO: 209.
16. The fusion molecule of claim 8 , wherein the antibody or antigen-binding fragment comprises a heavy chain variable region having the sequence set forth in SEQ ID NO: 203 and a light chain variable region having the sequence set forth in SEQ ID NO: 209.