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 subject having an autoimmune disorder a therapeutic composition comprising a pharmaceutically acceptable carrier and at least one human, humanized or chimeric anti-CD74 antibody which binds to human CD74 or antigen-binding fragment thereof, or anti-CD74 fusion protein. 
     
     
         2 . The method of  claim 1 , wherein the therapeutic composition comprises an unconjugated anti-CD74 antibody, an anti-CD74 fusion protein, a single chain anti-CD74 antibody or an anti-CD74 immunoconjugate. 
     
     
         3 . The method of  claim 2 , wherein the therapeutic composition comprises an anti-CD74 immunoconjugate in which the anti-CD74 antibody is conjugated to an immunomodulator, a therapeutic radioisotope, a cytotoxic agent or a drug. 
     
     
         4 . The method of  claim 2 , wherein the therapeutic composition comprises an anti-CD74 immunoconjugate in which the anti-CD74 antibody is conjugated to a drug that acts on B-cells, plasma cells or T-cells. 
     
     
         5 . The method of  claim 2 , wherein the therapeutic composition comprises an anti-CD74 immunoconjugate in which the anti-CD74 antibody is conjugated to doxorubicin, a toxin, a cytokine, a stem cell growth factor, a lymphotoxin, a hematopoietic factor, a colony stimulating factor (CSF), an interferon (IFN), erythropoietin, thrombopoietin, a phototherapeutic agent, an alkaloid, a camptothecin, an anthracycline, a ribonuclease, an onconase, Pseudomonas exotoxin or a tumor necrosis factor. 
     
     
         6 . The method of  claim 2 , wherein the therapeutic composition comprises an anti-CD74 immunoconjugate in which the anti-CD74 antibody is conjugated to a therapeutic radioisotope selected from the group consisting of 90Y 111 In 131 I  188 Re,  177 Lu, and  212   Pb . 
     
     
         7 . The method of  claim 2 , wherein the therapeutic composition comprises an anti-CD74 immunoconjugate in which the anti-CD74 antibody is conjugated to TNF-a. 
     
     
         8 . The method of  claim 2 , wherein the therapeutic composition comprises an anti-CD74 immunoconjugate in which the anti-CD74 antibody is conjugated to interferon-a. 
     
     
         9 . The method of  claim 1 , wherein the anti-CD74 antibody is a chimeric antibody. 
     
     
         10 . The method of  claim 1 , wherein the anti-CD74 antibody is a humanized antibody. 
     
     
         11 . The method of  claim 1 , additionally comprising administering a secondary therapeutic, wherein the anti-CD74 antibody and the secondary therapeutic are administered concurrently or sequentially. 
     
     
         12 . The method of  claim 11 , wherein the secondary therapeutic is a drug. 
     
     
         13 . The method of  claim 12 , wherein the drug is a drug that acts on B-cells, plasma cells or T-cells. 
     
     
         14 . The method of  claim 11 , wherein the secondary therapeutic is an immunoconjugate with an antibody that targets a B-cell. 
     
     
         15 . The method of  claim 11 , wherein the secondary therapeutic is an anti-CD74 immunoconjugate.