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Reagents and treatment methods for autoimmune diseases

a technology of autoimmune diseases and antibodies, applied in the field of anti-anticd22 monoclonal antibodies, can solve problems such as significant morbidity and disability

Inactive Publication Date: 2008-05-22
DUKE UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0025]The treatment methods of the present invention may be performed without any further treatment of malignant B cells or autoimmune disease. With respect to B-cell malignancy, the treatment method of the present invention typically provides improved cure rate and / or increased survival and / or superior tumor volume reduction when compared to no treatment, combination treatment with the same antibody and radioimmunotherapy, or with radioimmunotherapy alone.

Problems solved by technology

Autoimmune diseases as a whole cause significant morbidity and disability.

Method used

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  • Reagents and treatment methods for autoimmune diseases
  • Reagents and treatment methods for autoimmune diseases
  • Reagents and treatment methods for autoimmune diseases

Examples

Experimental program
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example 1

Production of Anti-CD22 Monoclonal Antibodies

[0122]Monoclonal antibodies (mAbs) HB22-7 (IgG2b), HB22-23 (IgG2a) 1HB22-33 (IgM), HB22-5 (IgG2a), HB22-13 (IgG2a), HB22-22 (IgA), and HB22-196 were produced according to the method of Engel et al., J Immunol 15:4710 (1993) and U.S. Pat. No. 5,484,892. See, also Tuscano et al, Blood 94:1382-1392 (1999). However, other methods may be used. Briefly, the HB22 mAbs were produced via hybridoma techniques using a mouse pre-B cell line 300.19, stably transfected with full length CD22 cDNA, as the immunogen. More specifically, thirty-three mAbs reactive with CD22 were generated by the fusion of NS-1 myeloma cell with spleen cells from Balb / c mice immunized three times with a mouse pre-B cell line, 300.19, stably transfected with a full-length CD22 cDNA. Hybridomas producing mAb reactive with mouse L cells transfected with CD22 cDNA, but not with untransfected cells, were cloned twice and used to generate supernatant or ascites fluid. mAb isotypes...

example 2

Raji and Ramos Lymphoma Xenograft Trials

[0124]This example describes the results from our independent Raji and Ramos lymphoma xenograft trials. Nude mice xenografts are important tools for preclinical evaluations. Nude mice bearing human non-Hodgkin's lymphoma (NHL) xenografts utilizing the lymphoma cell lines Raji and Ramos have proven utility for evaluating efficacy for treatment of NHL. (Buchsbaum et al., Cancer Res. 52(23):6476-6481 (1992) and Flavell et al., Cancer Res. 57:4824-4829 (1997)).

[0125]Materials and Methods

[0126]Reagents. Carrier-free 90Y (Pacific Northwest National Laboratory, Richland, Wash.) and 111In (Nordion, Kanata, Ontario, Canada) were purchased as chlorides in dilute HCl. Lym-1 (Techniclone, Inc Tustin, Calif.) is an IgG2a mAb generated in mice immunized with human Burkitt's lymphoma cell nuclei. Lym-1 recognizes a cell surface 31-35 kD antigen on malignant B cells, and reacts with greater than 80% of human B cell NHL. Lym-1 purity was assessed according to ...

example 3

Sequence Analysis of Anti-CD22 Antibodies

[0156]VH and Light Chain Gene Utilization

[0157]Cytoplasmic RNA was extracted from 1−10×105 hybridoma cells using the RNeasy Mini Kit (Qiagen Chatsworth, Calif.). First strand cDNA was synthesized from cytoplasmic RNA using oligo-dT primers (dT18) and a Superscript Kit (Gibco BRL, Gaithersburg, Md.). One μl of cDNA solution was used as template for PCR amplification of VH genes. PCR reactions were carried out in a 100-μl volume of a reaction mixture composed of 10 mM Tris-HCl (pH 8.3), 50 mM KCl, 1.5 mM MgCl2, 200 μM dNTP (Perkin Elmer, Foster City, Calif.), 50 μmol of each primer, and 5 U of Taq polymerase (ISC Bioexpress, Kaysville, Utah). Amplification was for 30 cycles (94° C. for 1 min, 58° for 1 min, 72° C. for 1 min; Thermocycler, Perkin Elmer). VH genes were amplified using a promiscuous sense 5′ VH primer (Ms VHE: 5′ GGG AAT TCG AGG TGC AGC TGC AGG AGT CTG G 3′; SEQ ID NO: 2) as previously described (Kantor et al., J. Immunol. 158:117...

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Abstract

The invention concerns treatment methods using anti-CD22 monoclonal antibodies with unique physiologic properties. In particular, the invention concerns methods for the treatment of B-cell malignancies and autoimmune diseases by administering an effective amount of a blocking anti-CD22 monoclonal antibody specifically binding to the first two Ig-like domains, or to an epitope within the first two Ig-like domains of native human CD22 (hCD22).

Description

[0001]This application is a continuation of U.S. patent application Ser. No. 10 / 372,481, filed Feb. 21, 2003, which claims priority from U.S. Provisional Application Ser. No. 60 / 359,419, filed Feb. 21, 2002 and U.S. Provisional Application Ser. No. 60 / 420,472, filed Oct. 21, 2002, each of which is incorporated herein by reference in its entirety.[0002]The present invention was made with the support of Grant No. CA 81776 from the National Institutes of Health. The United States government has certain rights in this invention.BACKGROUND OF THE INVENTION[0003]1. Field of the Invention[0004]The present invention concerns the therapeutic use of certain anti-CD22 monoclonal antibodies with unique physiologic properties. More specifically, the invention concerns methods of treating B-cell malignancies, such as lymphomas and leukemias, and autoimmune diseases with blocking anti-CD22 antibodies having unique pro-apoptotic properties.[0005]2. Description of the Related Art[0006]CD22 is a memb...

Claims

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Application Information

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IPC IPC(8): A61K39/395C07K16/28A61P37/00A61B5/055C12N15/09A61P35/00A61P35/02A61P37/02C07K16/42C12N15/13C12P21/08G01N24/08
CPCA61K39/39533A61K2039/505C07K16/2803C07K2316/96C07K2317/56A61K2300/00C07K2317/73C07K2317/76A61P1/00A61P1/04A61P13/02A61P13/12A61P17/00A61P17/02A61P17/06A61P19/00A61P19/02A61P19/04A61P21/00A61P21/04A61P25/00A61P27/02A61P29/00A61P35/00A61P35/02A61P37/00A61P37/02A61P37/04A61P37/06A61P37/08A61P5/00A61P5/14A61P5/16A61P7/00A61P7/02A61P7/04A61P7/06A61P9/00A61P9/08A61P9/10A61P3/10A61K39/395C07K16/28C12N15/11
Inventor TEDDER, THOMAS F.
Owner DUKE UNIV
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