Immunotherapy of autoimmune disorders using antibodies which target b-cells

Abstract

Antibodies that bind with a B-cell antigen provide an effective means to treat autoimmune disorders. Antibodies and fragments, which may be conjugated or naked, are used alone or in multimodal therapies. The antibodies may be bispecific antibodies which may be produced recombinantly as fusion proteins, or as hybrid, polyspecific antibodies.

1 . A method for treating an autoimmune disorder comprising administering to a human subject having an autoimmune disorder an effective amount of a murine, chimeric, human, or humanized anti-CD22 LL2 antibody (ATCC Accession No. PTA-6735) or antigen-binding fragment thereof. 
     
     
         2 . The method of  claim 1 , wherein the anti-CD22 antibody or fragment thereof is conjugated to at least one therapeutic agent. 
     
     
         3 . The method of  claim 2 , wherein the therapeutic agent is selected from the group consisting of drugs, toxins, enzymes, hormones, cytokines, immunomodulators, boron compounds, therapeutic radioisotopes, antibodies and antigen-binding antibody fragments. 
     
     
         4 . The method of  claim 3 , wherein the radioisotope is selected from the group consisting of  198 Au,  32 P,  125 I,  131 I,  90 Y,  186 Re,  188 Re,  67 Cu and  211 At. 
     
     
         5 . The method of  claim 3 , wherein the drug is selected from the group consisting of methotrexate, phenyl butyrate, bryostatin, cyclophosphamide, etoposide, bleomycin, doxorubicin, carmustine, vincristine, procarbazine, dexamethasone, leucovorin, prednisone, maytansinoid, calicheamicin, rapamycin, leflunomide, FK506, fludarabine, azathioprine, mycophenolate and cyclosporine. 
     
     
         6 . The method of  claim 3 , wherein the toxin is selected from the group consisting of ricin, abrin, ribonuclease, DNase I, Staphylococcal enterotoxin-A, pokeweed antiviral protein, gelonin, diphtheria toxin,  Pseudomonas  exotoxin,  Pseudomonas  endotoxin and onconase. 
     
     
         7 . The method of  claim 3 , wherein the cytokine is selected from the group consisting of IL-1, IL-2, TNF-α and GM-CSF. 
     
     
         8 . The method of  claim 2 , further comprising administering at least one secondary therapeutic agent to the subject before, simultaneously with or after the anti-CD22 antibody or fragment thereof. 
     
     
         9 . The method of  claim 8 , wherein the secondary therapeutic agent is selected from the group consisting of drugs, toxins, enzymes, hormones, cytokines, immunomodulators, boron compounds, therapeutic radioisotopes, antibodies and antigen-binding antibody fragments. 
     
     
         10 . The method of  claim 9 , wherein the secondary therapeutic agent is an antibody or antigen-binding antibody fragment that binds to a B-cell, a T-cell, a plasma cell, a macrophage or an inflammatory cytokine. 
     
     
         11 . The method of  claim 9 , wherein the secondary therapeutic agent is an antibody or antigen-binding antibody fragment that binds to a B-cell antigen. 
     
     
         12 . The method of  claim 11 , wherein the B-cell antigen is selected from the group consisting of CD19, CD20, CD22, CD74 and HLA-DR. 
     
     
         13 . The method of  claim 1 , wherein the anti-CD22 antibody is a naked antibody. 
     
     
         14 . The method of  claim 13 , further comprising administering at least one therapeutic agent to the subject before, concurrently with or after the anti-CD22 antibody. 
     
     
         15 . The method of  claim 14 , wherein the therapeutic agent is selected from the group consisting of drugs, toxins, enzymes, hormones, cytokines, immunomodulators, boron compounds, therapeutic radioisotopes, antibodies and antibody fragments. 
     
     
         16 . The method of  claim 15 , wherein the radioisotope is selected from the group consisting of  198 Au,  32 P,  125 I,  131 I,  90 Y,  186 Re,  188 Re,  67 Cu and  211 At. 
     
     
         17 . The method of  claim 15 , wherein the drug is selected from the group consisting of methotrexate, phenyl butyrate, bryostatin, cyclophosphamide, etoposide, bleomycin, doxorubicin, carmustine, vincristine, procarbazine, dexamethasone, leucovorin, prednisone, maytansinoid, calicheamicin, rapamycin, leflunomide, FK506, fludarabine, azathioprine, mycophenolate and cyclosporine. 
     
     
         18 . The method of  claim 15 , wherein the toxin is selected from the group consisting of ricin, abrin, ribonuclease, DNase I, Staphylococcal enterotoxin-A, pokeweed antiviral protein, gelonin, diphtheria toxin,  Pseudomonas  exotoxin,  Pseudomonas  endotoxin and onconase. 
     
     
         19 . The method of  claim 15 , wherein the cytokine is selected from the group consisting of IL-1, IL-2, TNF-α and GM-CSF. 
     
     
         20 . The method of  claim 14 , wherein the therapeutic agent is an antibody or antigen-binding antibody fragment that binds to a B-cell, a T-cell, a plasma cell, a macrophage or an inflammatory cytokine. 
     
     
         21 . The method of  claim 20 , wherein the therapeutic agent is an antibody or antigen-binding antibody fragment that binds to a B-cell antigen. 
     
     
         22 . The method of  claim 21 , wherein the B-cell antigen is selected from the group consisting of CD19, CD20, CD22, CD74 and HLA-DR. 
     
     
         23 . The method of  claim 1 , wherein said anti-CD22 antibody or fragment thereof is administered parenterally in a dosage of from 20 to 2000 mg per dose. 
     
     
         24 . The method of  claim 23 , wherein said subject receives said anti-CD22 antibody or fragment thereof in repeated parenteral dosages. 
     
     
         25 . The method of  claim 1 , wherein said autoimmune disease is selected from the group consisting of acute idiopathic thrombocytopenic purpura, chronic idiopathic thrombocytopenic purpura, dermatomyositis, Sydenham's chorea, myasthenia gravis, systemic lupus erythematosus, lupus ephritis, rheumatic fever, polyglandular syndromes, bullous pemphigoid, diabetes mellitus, Henoch-Schonlein purpura, post-streptococcal nephritis, erythema nodosum, Takayasu's arteritis, Addison's disease, rheumatoid arthritis, multiple sclerosis, sarcoidosis, ulcerative colitis, erythema multiforme, IgA nephropathy, polyarteritis nodosa, ankylosing spondylitis, Goodpasture's syndrome, thromboangitis obliterans, Sjogren's syndrome, primary biliary cirrhosis, Hashimoto's thyroiditis, thyrotoxicosis, scleroderma, chronic active hepatitis, polymyositis/dermatomyositis, polychondritis, pemphigus vulgaris, Wegener's granulomatosis, membranous nephropathy, amyotrophic lateral sclerosis, tabes dorsalis, giant cell arteritis/polymyalgia, pernicious anemia, rapidly progressive glomerulonephritis and fibrosing alveolitis. 
     
     
         26 . The method of  claim 1 , wherein said autoimmune disease is Sjogren's syndrome. 
     
     
         27 . The method of  claim 1 , wherein said autoimmune disease is systemic lupus erythematosus. 
     
     
         28 . The method of  claim 1 , wherein said autoimmune disease is rheumatoid arthritis. 
     
     
         29 . The method of  claim 1 , wherein said autoimmune disease is idiopathic thrombocytopenic purpura. 
     
     
         30 . The method of  claim 1 , wherein said autoimmune disease is multiple sclerosis. 
     
     
         31 . The method of  claim 1 , wherein said autoimmune disease is diabetes. 
     
     
         32 . The method of  claim 1 , wherein said autoimmune disease is diabetes. 
     
     
         33 . The method of  claim 1 , wherein said autoimmune disease is arteritis. 
     
     
         34 . The method of  claim 1 , wherein said autoimmune disease is thyrotoxicosis. 
     
     
         35 . The method of  claim 1 , wherein said autoimmune disease is pemphigus vulgaris.