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Combined therapeutic use of antibodies and endoglycosidases

A serum antibody, therapeutic antibody technology, applied in the direction of antibody medical components, antibodies, immunoglobulins, etc., can solve problems such as the availability of unbound receptors

Inactive Publication Date: 2018-10-09
ハンサバイオファルマアクチボラゲット
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0015] While engineering antibodies to exhibit enhanced FcR binding has yielded some improvements in the recruitment of cellular immune cells, these approaches are inherently limited by the availability of unbound receptors

Method used

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  • Combined therapeutic use of antibodies and endoglycosidases
  • Combined therapeutic use of antibodies and endoglycosidases
  • Combined therapeutic use of antibodies and endoglycosidases

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0200] Example 1: Decreased binding of serum IgG to FcγRIIIa increases binding of resistant therapeutic antibodies

[0201] To demonstrate that EndoS can be used to reduce the binding of serum IgG to FcγRIIIa, the following experiments were performed. High binding microtiter plates (3690, Corning, NY, U.S.A.) were coated overnight at 4°C with 2.5 μg / mL of FcγRIIIa (158Val variant; R&D systems, Minneapolis, U.S.A.) in PBS. Coated plates were washed with PBS containing 0.05% Tween 20 (Sigma-aldrich, U.S.A.) and blocked with 3% BSA in PBS for 2 hours at room temperature. Then add human serum (H4522, Sigma-Aldrich, U.S.A.) or carry Man 9 GlcNAc 2 or Man 5 GlcNAc 2 serial dilutions of recombinant human IgG1 glycoforms (initial concentration 0.1 mg / mL in PBS) and allowed to bind for 2 hours at room temperature. Plates were washed five times with PBS containing 0.05% Tween and binding was detected using a Fab fragment specific for murine IgG Fab conjugated to HRP (ab98659, Abcam...

Embodiment 2

[0221] Example 2: Mouse Model

[0222] Cells from the cell line SKBR3 (a cell line highly expressing HER2) were introduced subcutaneously into mice. EndoS and a therapeutic antibody against HER2 (such as Herceptin) resistant to EndoS are introduced intravenously at a dose of 30 mg / Kg per week for 4 weeks. Control mice did not receive (i) Endo S or (ii) therapeutic antibody. The size of the resulting tumors was measured with calipers.

Embodiment 3

[0223] Example 3: Delayed Administration of Therapeutic Antibodies

[0224] Breast cancer subjects were treated intravenously with 15 mg EndoS in saline solution. Monitor patient IgG glycosylation levels (deglycosylation of IgG reduces IgG mass) by purifying patient IgG samples and estimating IgG mass by SDS-PAGE.

[0225] After a 2-day delay, subjects were treated intravenously with 2 mg of therapeutic antibody / kg body weight of trastuzumab.

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Abstract

The invention relates to compositions comprising therapeutic antibodies, and uses and methods for increasing the potency of therapeutic antibodies. In particular, the invention provides a compositioncomprising (i) an agent which reduces Fc receptor binding of endogenous serum antibodies, and (ii) a therapeutic antibody, preferably a therapeutic antibody which is resistant to the agent. The therapeutic antibody may be administered to the subject after a set time interval, or the blood of the subject may be treated with the agent prior to administration of the therapeutic antibody.

Description

[0001] This application is a divisional application, the application number of the original application is 201380012248.3, the application date is January 25, 2013, and the invention name is "combined therapeutic application of antibody and endoglycosidase". technical field [0002] The present invention relates to compositions comprising therapeutic antibodies and uses and methods for increasing the efficacy of therapeutic antibodies. In particular, the present invention provides a composition comprising: (i) an agent that reduces binding of Fc receptors to endogenous serum antibodies, and (ii) a therapeutic antibody, preferably reactive to said agent resistant therapeutic antibodies. The therapeutic antibody may be administered to the subject after a set time interval, or the subject's blood may be treated with the agent prior to administration of the therapeutic antibody. Background technique [0003] Historically, the original purpose of using antibodies, especially mon...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/395A61P35/00A61P31/00A61P37/02A61K38/47
CPCA61K39/39558C12Y302/01096A61K2039/505C07K2317/41A61K38/47A61P15/00A61P31/00A61P31/04A61P35/00A61P35/02A61P37/00A61P37/02A61P43/00A61K2300/00A61K39/3955
Inventor M·D·M·克里斯潘C·N·斯坎伦
Owner ハンサバイオファルマアクチボラゲット
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