Humanized anti-ErbB2 antibodies and treatment with anti-ErbB2 antibodies

A humanized antibody, antibody technology, applied in the direction of antibodies, anti-tumor drugs, chemical instruments and methods, etc.

Inactive Publication Date: 2002-09-18
GENENTECH INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0011] Although EGF and TGFα do not bind ErbB2, EGF stimulates EGFR and ErbB2 to form a heterodimer, which activates EGFR and leads to transphosphorylation of ErbB2 in the heterodimer

Method used

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  • Humanized anti-ErbB2 antibodies and treatment with anti-ErbB2 antibodies

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Experimental program
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Effect test

preparation example

[0260] Controlled release formulations can also be prepared. Suitable examples of controlled-release preparations include semi-permeable matrices of solid hydrophobic polymers containing antibodies, which matrices are shaped articles such as films or microcapsules. Examples of controlled-release preparations include polyesters, hydrogels (such as poly(2-hydroxyethyl-methacrylate) or poly(vinyl alcohol), polylactide (US Patent 3,773,919), L-glutamic acid and gamma ethyl -L-glutamate copolymer, non-degradable ethylene ethyl acetate, degradable lactic acid-glycolic acid copolymer such as LUPRONDEPOT TM (Injectable microspheres composed of lactic acid-glycolic acid copolymer and leuprolide acetate), and poly-D-(-)-3-hydroxybutyric acid.

[0261] The preparation for in vivo administration must be sterile. This can be easily achieved by filtration through a sterile filter.

[0262] V. Treatment with anti-ErbB2 antibodies

[0263] According to the present invention, anti-ErbB2 antibodies...

Embodiment 1

[0323] Preparation and identification of monoclonal antibody 2C4

[0324]According to the method described in Fendly et al., Cancer Research 50: 1550-1558 (1990), murine monoclonal antibodies 2C4, 7F3, and 4D5 that specifically bind to the extracellular domain of ErbB2 were prepared. In short, NIH 3T3 / HER2-3400 cells (about expression 1×10 5 ErbB2 molecule / cell) and used it to immunize BALB / c mice. In 0, 2, 5 and 7 weeks, mice were injected intraperitoneally with 10 7 Cells (in 0.5ml PBS). Give a specific antiserum (which can be combined with 32 P-labeled ErbB2 immunoprecipitation) mice were intraperitoneally injected with wheat germ agglutinin-Sepharose (WGA) purified ErbB2 membrane extract. Then 0.1ml of ErbB2 preparation was injected intravenously, and the spleen cells were fused with the mouse myeloma cell line X63-Ag8.653.

[0325] The ErbB2 binding of the supernatant of hybridoma cells was screened by ELISA and radioimmunoprecipitation.

[0326] A competitive binding assay (...

Embodiment 2

[0336] Monoclonal antibody 2C4 blocks the HRG-dependent binding of ErbB2 to ErbB3

[0337] Co-immunoprecipitation was used to detect the ability of ErbB3 to bind ErbB2. 1.0×10 6 MCF7 or SK-BR-3 cells were seeded in a 6-well tissue culture plate and allowed to adhere overnight. The culture medium was 50:50 DMEM / Ham's F12 containing 10% fetal bovine serum (FBS) and 10mM HEPES (pH 7.2) Base (growth medium). Before the start of the experiment, the cells were starved and cultured in serum-free growth medium for 2 hours.

[0338]Simply wash the cells with PBS, and then use 100 nM of the indicated antibody (diluted in 0.2% w / v bovine serum albumin (BSA) RPMI medium (pH 7.2) (binding buffer) containing 10 mM HEPES) or just The cells were incubated with binding buffer (control). After 1 hour at room temperature, HRG was added to half of the wells to a final concentration of 5nM(+). Add a similar volume of binding buffer (-) to the other wells. Continue to incubate for approximately 10 minu...

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Abstract

This application describes humanized anti-ErbB2 antibodies, and methods of treating cancer with anti-ErbB2 antibodies, such as humanized anti-ErbB2 antibodies.

Description

Invention field [0001] The present invention relates to humanized anti-ErbB2 antibodies and methods for treating cancer with anti-ErbB2 antibodies such as humanized anti-ErbB2 antibodies. Background of the invention [0002] The ErbB family of receptor tyrosine kinases are important mediators in cell growth, differentiation and survival. The receptor family includes 4 different members, namely epidermal growth factor receptor (EGFR or ErbB1), HER2 (ErbB2 or p185 neu ), HER3 (ErbB3) and HER4 (ErbB4 or tyro2). [0003] There is evidence that EGFR encoded by the erbB1 gene is related to human malignancies. Especially in breast cancer, bladder cancer, lung cancer, head tumor, neck tumor, gastric cancer, and glioblastoma, the increased expression of EGFR has been observed. Increased EGFR receptor expression is usually associated with increased production of EGFR ligand, transforming growth factor alpha (TGF-α) in the same cancer cell, leading to activation of the rec...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61K31/337A61K31/429A61K31/437A61K31/4985A61K31/513A61K31/555A61K33/243A61K39/395A61K47/48A61P35/00A61P43/00C07K16/32
CPCA61K2039/505A61K2039/507C07K16/32C07K2317/24C07K2317/73C07K2317/76A61K47/6809A61P35/00A61P43/00A61K39/395
Inventor 卡梅利亚·W·亚当斯伦纳德·G·普雷斯塔马克·斯利科斯基
Owner GENENTECH INC
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