Humanized anti-CD22 antibody
Disclosed are humanized RFB4 antibodies or antigen-binding fragments thereof. therapy of B-cell associated diseases, such as B-cell malignancies, autoimmune disease and immune dysfunction disease. Preferably, hRFB4 comprises the light and heavy chain RFB4 CDR sequences with human antibody FR and constant region sequences, along with heavy chain framework region (FR) amino acid residues Q1, F27, V48, A49, F68, R98, T117 and light chain residues L4, S22, K39, G100, V104, and K107. More preferably, the heavy and light chain variable region sequences of hRFB4 comprise SEQ ID NO:7 and SEQ ID NO:8, respectively. In certain embodiments, trogocytosis (antigen shaving) induced by hRFB4 plays a significant role in determining antibody efficacy and disease responsiveness for treatment of B-cell diseases, such as hematopoietic cancers, immune system dysfunction and/or autoimmune disease.
1. A method of treating an autoimmune disease, comprising administering to a subject with an autoimmune disease a humanized anti-CD22 antibody or antigen-binding fragment thereof comprising the heavy chain variable region amino acid sequence SEQ ID NO:7 and the light chain variable region amino acid sequence SEQ ID NO:8, wherein the autoimmune disease is selected from the group consisting of systemic lupus erythematosus (SLE), primary Sjogren's syndrome, and rheumatoid arthritis.
2. The method of claim 1 , wherein the anti-CD22 antibody or fragment thereof is capable of reducing the levels of one or more proteins on the surface of B cells by trogocytosis, wherein the proteins are selected from the group consisting of CD19, CD20, CD21, CD22 and CD79b.
3. The method of claim 1 , wherein the anti-CD22 antibody fragment is selected from the group consisting of a F(ab′) 2 , F(ab) 2 , Fab′, Fab, Fv, scFv, diabody, and half-molecule of IgG4.
4. The method of claim 1 , wherein the anti-CD22 antibody is an IgG antibody.
5. The method of claim 1 , wherein the anti-CD22 antibody or fragment thereof is an unconjugated antibody or fragment thereof.
6. The method of claim 2 , wherein the anti-CD22 antibody or fragment thereof induces trogocytosis of CD19 from B cells and induces depletion of circulating B cells by less than 50%.