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TSPAN 33 is a candidate for antibody targeted therapy for the treatment of B cell hodgkin lymphomas

A technology for Hodgkin's lymphoma and lymphoma, applied in the direction of antibodies, anti-receptors/cell surface antigens/cell surface determinant immunoglobulins, extracellular fluid diseases, etc.

Inactive Publication Date: 2016-04-13
RGT UNIV OF CALIFORNIA +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, normal B cells also express CD20, so although antibody therapy targeting CD20 eliminates most of the tumor cells, this treatment also removes normal B cells which also express CD20 (15)

Method used

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  • TSPAN 33 is a candidate for antibody targeted therapy for the treatment of B cell hodgkin lymphomas
  • TSPAN 33 is a candidate for antibody targeted therapy for the treatment of B cell hodgkin lymphomas
  • TSPAN 33 is a candidate for antibody targeted therapy for the treatment of B cell hodgkin lymphomas

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Experimental program
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Embodiment 1

[0131] We have identified Tspan33 as a gene encoding a transmembrane protein that exhibits a restricted expression pattern that includes expression in activated B cells. TSPAN33 is a member of the tetraspanin family. TSPAN33 is not expressed in resting B cells, but is strongly induced in activated primary human B cells. Human 2E2 cells, an activated and differentiated Burkitt's lymphoma-derived B cell model, also upregulate TSPAN33 upon activation. TSPAN33 is expressed in a variety of lymphomas including Hodgkin's lymphoma and diffuse large B-cell lymphoma. TSPAN33 is also expressed in some autoimmune diseases in which B cells are involved in the disease, including patients with rheumatoid arthritis, systemic lupus erythematosus (SLE), and from MRL / Fas lpr / lpr In the spleen B cells of mice (mouse SLE model). We conclude that TSPAN33 can be used as a diagnostic biomarker or target for therapeutic antibodies to treat certain B-cell lymphomas or autoimmune diseases.

[0132] ...

Embodiment 2

[0134] introduction

[0135] The discovery and characterization of lineage-specific markers has helped to identify the subset of cells that underlie the complexity of the immune system. Lymphocyte populations are routinely differentiated using cell surface markers such as CD3ε (a pan-T cell marker), CD4 (helper T cells), CD8 (cytotoxic T cells), and B220 / CD45R (B cells) [1 -2]. Advances in flow cytometry labeling techniques have enabled the characterization of CD4 subtypes (Th1, Th2, Th17, and Treg cells) based on the detection of lineage-specific transcription factors [3]. Regulatory 'B10 cells' discovery based on CD1d hi CD5 + and the identification of a small subset of IL-10-secreting B cells [4-6]. Furthermore, lineage-specific surface markers such as the B-cell marker CD20 represent useful targets for the development of therapeutic mAbs that have been shown to be effective against various lymphoma and autoimmune diseases such as rheumatoid arthritis (RA 1 )[7-8].

...

Embodiment 3

[0143] method

[0144] microarray analysis

[0145] The generation of the Body Index Database of Gene Expression (BIGE) has been described [9-10]. Briefly, total RNA was obtained from 4 male and 4 female human donors between 3-5 hours postmortem, or using commercially available human tissue RNA (Clontech, Palo Alto, CA). , PaloAlto, CA)) to expand total RNA. Genome-wide gene expression data were obtained using the Affymetrix Human Genome U133Plus2.0 Gene Array (Affymetrix, Santa Clara, CA) and analyzed in ArrayAssistsoftware (IobionLabs, La Jolla, CA). (IobionLabs, LaJolla, CA)) for data normalization and aggregation.

[0146] qRT-PCR

[0147] use Kit, RNA isolation from human cell lines / cells or tissues according to manufacturer's instructions (Qiagen, CA). use Reverse transcription (Quick and Precision, CA) converts RNA to cDNA. Use Roche 480 Real Time PCR System, qPCR was performed with probes designed to detect TSPAN33, CD19, CD20, CD138, and GAPDH (Roche, Pl...

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Abstract

A method of treating a disease associated with activated B lymphocytes expressing Tetraspanin 33 (TSPAN33 / BAAM). The disease can be, for example, lymphoma or an immune disease. The method includes administering an anti-TSPAN33 / BAAM antibody to a patient in need of such treatment in an amount effective to treat the disease. Methods of purifying activated B cells and identifying activated and / or diseased B cells are also provided.

Description

[0001] Statement Regarding Federally Sponsored Research or Development [0002] This invention was made with government support under grant number R21AI096278 from the National Institutes of Health. The government has certain rights in this invention. [0003] background technical field [0004] The present invention relates to the protein TSPAN33 expressed in activated B cells. Background technique [0005] B cells are lymphocytes that coordinate the humoral response of the adaptive immune system (1). Unlike T cells, which mature in the thymus, B cells arise in the bone marrow, where they mature into mature naive B cells (1). B cells are only responsible for secreting antibodies that recognize foreign antigens or self-antigens in the case of autoimmune diseases. Antibodies are divided into subtypes that determine both their location and function, such as IgA involved in protecting mucosal surfaces. Certain types of lymphomas have a B-cell origin. B-cell lymphomas have...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/395
CPCA61K2039/505C07K2317/76C07K16/28A61P1/04A61P1/14A61P1/16A61P11/00A61P17/00A61P17/06A61P19/02A61P25/00A61P29/00A61P35/00A61P35/02A61P37/02A61P37/06A61P37/08A61P43/00A61P5/14A61P7/00A61P9/00C07K16/3061C12Q1/6883C12Q2600/158G01N33/56972G01N2333/705
Inventor 艾伯特·兹洛特尼克彼得·海维兹万·鲁胡安·巴布洛·佛洛雷斯
Owner RGT UNIV OF CALIFORNIA
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