Granulocyte-macrophage colony-stimulating factor (GM-CSF) neutralizing antibodies
The invention provides a GM-CSF neutralizing human monoclonal antibody, 1783J22, as well as methods of making and use thereof. The monoclonal antibody is further characterized by its ability to bind epitopes from GM-CSF proteins of multiple species.
1. An isolated anti-GM-CSF antibody, wherein the antibody comprises a V H CDR1 region comprising the amino acid sequence of FPFHKYTMT (SEQ ID NO: 8); a V H CDR2 region comprising the amino acid sequence of VSGVNGKTYYSPSVRG (SEQ ID NO: 9); a V H CDR3 region comprising the amino acid sequence of GPGGHLHYYYGLDV (SEQ ID NO: 10); a V L CDR1 region comprising the amino acid sequence of RASQAINNYVA (SEQ ID NO: 14); a V L CDR2 region comprising the amino acid sequence of GASNLQP (SEQ ID NO: 15); and a V L CDR3 region comprising the amino acid sequence of QNYFGYPLT (SEQ ID NO: 16).
2. An isolated anti-GM-CSF antibody, wherein the antibody comprises a V H CDR1 region comprising the amino acid sequence of GFPFHKYTMT (SEQ ID NO: 11); a V H CDR2 region comprising the amino acid sequence of VSGVNGKTY (SEQ ID NO: 12); a V H CDR3 region comprising the amino acid sequence of GPGGHLHYYYGLDV (SEQ ID NO: 10); a V L CDR1 region comprising the amino acid sequence of RASQAINNYVA (SEQ ID NO: 14); a V L CDR2 region comprising the amino acid sequence of GASNLQP (SEQ ID NO: 15); and a V L CDR3 region comprising the amino acid sequence of QNYFGYPLT (SEQ ID NO: 16).
3. An isolated fully human monoclonal anti-GM-CSF antibody comprising a heavy chain sequence comprising the amino acid sequence SEQ ID NO: 2 and a light chain sequence comprising amino acid sequence SEQ ID NO: 5.
4. A composition comprising the antibody of claim 1 , 2 , or 3 and a pharmaceutically-acceptable carrier.
5. The antibody of claim 1 , 2 , or 3 , wherein the antibody is operably-linked to a therapeutic agent or a detectable label.
6. The composition of claim 4 , wherein the antibody is operably-linked to a therapeutic agent or a detectable label.
7. The composition of claim 4 , further comprising a second anti-GM-CSF antibody.
8. A B cell clone expressing the antibody of claim 1 , 2 , or 3 .
9. A method of inhibiting a biological activity of GM-CSF in a subject comprising administering to the subject the composition of claim 4 .
10. The method of claim 9 , wherein the subject has an infectious disease, an inflammatory disease, an autoimmune disorder, Alzheimer's Disease, vascular dementia (VAD), or cancer.
11. The method of claim 9 , wherein the subject has an inflammatory disease.
12. The method of claim 11 , wherein the inflammatory disease is selected from the group consisting of asthma, acute inflammation, chronic inflammation, type I diabetes, type II diabetes and all of the related pathologies, rheumatoid arthritis, autoimmune disease, inflammatory renal disease, inflammatory lung disorders such as asthma and chronic obstructive pulmonary disease (COPD), multiple sclerosis, and autoimmune encephalomyelitis.
13. The method of claim 9 , wherein the subject has cancer.
14. The method of claim 13 , wherein the cancer is selected from the group consisting of colon cancer, lung cancer, breast cancer, pancreatic cancer, leukemia, and juvenile myelomonocytic leukemia.
15. The method of claim 9 , further comprising administering a second anti-GM-CSF antibody.
16. The method of claim 15 , wherein the second antibody is administered simultaneously or sequentially with respect to the composition of claim 4 .
17. A therapeutic kit comprising the antibody of claim 1 , 2 , or 3 .
18. A therapeutic kit comprising the composition of claim 4 .
19. The method of claim 9 , wherein the subject has an infectious disease.
20. The method of claim 19 , wherein the infectious disease is selected from the group consisting of sepsis, severe acute respiratory syndrome (SARS; caused by SARS-associated coronavirus), hepatitis type B or type C, influenza, varicella, adenovirus, herpes simplex virus type I or type II, rinderpest, rhinovirus, echovirus, rotavirus, respiratory syncytial virus, papilloma virus, papova virus, cytomegalovirus, echinovirus, arbovirus, hantavirus, coxsachie virus, mumps virus, measles virus, rubella virus, polio virus, human immunodeficiency virus (HIV) type I or type II, Meningitis, Septic arthritis, Peritonitis, Pneumonia, Epiglottitis, E. coli , Hemolytic uremic syndrome, thrombocytopenia, to, Ebola, Staphylococcus A-E, Plasmodium, Malaria, Dengue, hemorrhagic fever, Leishmaniasis, Leprosy, Toxic shock syndrome, Streptococcal myositis , Gas gangrene, Mycobacterium , Pneumocystis, Pelvic inflammatory disease, Orchitis/epidydimitis, Legionella , Lyme disease Influenza A, Epstein-Barr Virus, Viral associated hemiaphagocytic syndrome, viral encephalitis, aseptic meningitis, mycoplasma, Neisseria, Legionella, Rickettsia , and Chlamydia.