Use of CD 23 antagonists for treatment of neoplastic disorders

An antagonist, tumor technology, applied in the direction of diseases, anti-tumor drugs, skin diseases, etc., can solve the problem of unsustainable remission

Inactive Publication Date: 2004-05-05
IDEC PHARM CORP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Unfortunately, these remissions from chemotherapy are usually not long-lasting

Method used

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  • Use of CD 23 antagonists for treatment of neoplastic disorders
  • Use of CD 23 antagonists for treatment of neoplastic disorders
  • Use of CD 23 antagonists for treatment of neoplastic disorders

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0138] Expression of CD23 in B lymphoma and B-CLL cells

[0139] The expression of CD23 in several lymphoma cell lines was determined by flow cytometry. More specifically, CD23 expression was evaluated by flow cytometry using an anti-CD23 PE-labeled antibody (BD Biosciences, Cat. No: 33615X). Relative fluorescence intensity (RFI) of antibody binding was determined by comparing the mean fluorescence intensity of anti-CD23-PE antibody bound to cells with that of PE-labeled calibration beads (QuantiBrite). CD23 relative expression was calculated as RFI(sample)÷RFI of SKW cells.

[0140] B lymphoma cell lines expressing CD20 and B7 (SKW, SB, Daudi, Raji, Ramos and DHL-4 cells) were cultured in complete medium. The complete medium was RPMI 1640 medium (Irvine Scientific, Santa Ana, CA), supplemented with 10% heat-inactivated FBS (Hyclone), 2 mM 1-glutamine, 100 units / ml penicillin, and 100 ug / ml streptomycin . The SKW cell line is Epstein-Barr virus (EBV) positive and...

Embodiment 2

[0148] Expression of CD23 in CLL cells

[0149] To demonstrate the clinical utility of the present invention, CD23 expression was measured in whole blood on several different CLL samples (31 patients) by flow cytometry. Flow cytometric analysis was performed essentially as described in Example 1 using appropriate reagents. In this regard, in CD19 + The expression of CD20 and CD23 was measured on positive sorted cells. Specifically, PE-labeled anti-CD20 (BD Biosciences / Pharmingen, Cat # 555623) and anti-CD23 (BD ​​Biosciences / Pharmingen, Cat # 33615X) monoclonal antibodies were used to detect CD20 and CD23 molecules, respectively.

[0150] In all patients, in CD19 + Both CD20 and CD23 antigens were detected in B cells, as shown in Table 2 below. Patients expressing high CD20 levels expressed varying degrees of CD23 antigen in their CLL samples. The expression level by CD19 + The percentage of cells and the mean fluorescence intensity (MFI) were determined. ...

Embodiment 3

[0154] IDEC-152 and CD23 + cell binding

[0155] In order to further confirm the advantages of the present invention, as described in the previous examples, the binding activity of IDEC-152 to CD23 on SKW lymphoma cells was measured by flow cytometry. As noted above, SKW cells can be used to provide a clinically relevant model of CD23+ malignancies including CLL. See the test results figure 1 , which showed the specific binding of Rituxan and IDEC-152 to SKW cells in a concentration-dependent manner. Binding activity was measured using mean fluorescence intensity, which showed that SKW cells bound substantially higher levels of anti-CD23 antibody than anti-CD20 antibody. This suggests that in certain cell lines and tumors, CD23 may present a higher epitope density than other markers such as CD20. As expected, an isotype-matched control antibody of irrelevant specificity (CE9.1, directed against CD4) did not bind SKW. This example, and in figure 1 The correspon...

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Abstract

The present invention provides methods and kits for treating neoplastic diseases, including the use of CD23 antagonists. The CD23 antagonists can be used alone or in combination with chemotherapeutic agents. In a particularly preferred embodiment, the CD23 antagonist may be used in the treatment of B-cell chronic lymphocytic leukemia (B-CLL).

Description

[0001] Cross References to Related Applications [0002] This application claims priority to the following patent applications: U.S. Serial No. 09 / 772,938, filed January 31, 2001; U.S. Serial No. 09 / 855,717, filed May 16, 2001; and U.S. Serial No. 09 / 985,646, filed on , each of which is incorporated herein by reference in its entirety. field of invention [0003] In a broader aspect, the invention relates to the use of CD23 antagonists for the treatment of neoplastic diseases. In a preferred embodiment, the present invention provides the use of an anti-CD23 antibody for immunotherapy of malignancies, including B-cell chronic lymphocytic leukemia (B-CLL). Background of the invention [0004] Patients with a wide variety of malignancies have benefited from advances in cancer treatment over the past few decades. Unfortunately, most patients eventually succumb to their disease despite modern therapies that greatly increase regression rates and prolong survival. Barriers to be...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/7076A61K38/00A61K39/395A61K45/06A61K51/00A61K45/00A61P7/00A61P31/18A61P35/00A61P35/02C07K16/28
CPCC07K16/2851A61K47/48561C07K16/2896C07K2317/732A61K2039/505C07K16/2827C07K16/2875C07K2317/24A61K47/6849A61P1/00A61P1/18A61P11/00A61P13/08A61P13/12A61P15/08A61P17/00A61P21/00A61P25/00A61P27/02A61P31/18A61P35/00A61P35/02A61P43/00A61P7/00A61P9/14A61K39/395
Inventor K·哈里哈兰N·翰纳G·R·布拉斯劳斯克N·帕圣
Owner IDEC PHARM CORP
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