Anti-HER2 (Trastuzumab biosimilar - IgG4 (S228P) isotype)

Human IgG4 (S228P) engineered monoclonal antibody (mAb) against HER2

Anti-HER2-Tra-hIgG4 (S228P) features the constant region of the human IgG4 (S228P) isotype and the variable region of trastuzumab. Trastuzumab is a humanized IgG1 monoclonal antibody that targets the HER2 receptor (human epidermal growth factor receptor 2 also known as HER2/neu) that is found on the cell membrane of epithelial cells.

HER2 plays an important role in normal cell growth and differentiation [1]. However, in certain types of cancers, particularly in breast and ovarian cancers, HER2 is over-expressed and causes uncontrollable cell proliferation. Binding of trastuzumab to HER2 results in cell death through different mechanisms including antibody-dependent cell-mediated cytotoxicity and phagocytosis [2, 3]. Trastuzumab has been approved by the FDA for the treatment of breast cancer.

Anti-HER2-Tra-hIgG4 (S228P) contains an engineered hinge region mutation (S228P) designed to prevent exchange of IgG4 molecules.

Anti-HER2-Tra-hIgG4 (S228P) was generated by recombinant DNA technology. It has been produced in Chinese hamster ovary (CHO) cells and purified by affinity chromatography with protein G. 

References:

1. Rubin I. & Yarden Y. 2001. The basic biology of HER2. Ann Oncol.12 Suppl 1:S3-8.
2. Collins DM. et al., 2012. Trastuzumab induces antibody-dependent cell-mediated cytotoxicity (ADCC) in HER-2-non-amplified breast cancer cell lines. Ann Oncol. 23(7):1788-95.
3. Petricevic B. et al., 2013. Trastuzumab mediates antibody-dependent cell- mediated cytotoxicity and phagocytosis to the same extent in both adjuvant and metastatic HER2/neu breast cancer patients. J Transl Med. 11:307.

Figures

Comparison of ADCC potency for native and engineered anti-HER2 antibody isotypes. Raji-HER2 cells were incubated with gradient concentrations of Anti-HER2-Tra mAbs, which feature the Trastuzumab variable region, or an Anti-β-galactosidase (β-Gal) mAb for 1 hour. Jurkat-Lucia™ NFAT-CD16 effector cells were then co-incubated with target cells for 6 hours. NFAT activation, reflecting the induced ADCC response, was assessed by determining Lucia luciferase activity in the supernatant using QUANTI-Luc™. Percentages of the maximal response normalized to the IgG1 isotype are shown.

Specifications

Specificity: Targets cells expressing HER2

Clonality: Monoclonal antibody

Clone: Trastuzumab (Anti-HER2-hIgG1, kappa)

Isotype: Human IgG4 (S228P), kappa

Control: Human IgG4 (S228P)

Source: CHO cells

Formulation: 0.2 µm filtered solution in 68 mM sodium phosphate buffer (pH 7.4) with 91 mM glycine, 5% w/v saccharose, and stabilizing agents

Purity: Purified by affinity chromatography with protein G

Tested application: Flow cytometry

Quality control:

• Binding of Anti-HER2-Tra-hIgG4 (S228P) to HER2 has been tested using flow cytometry.
• The complete sequence of this antibody has been verified.
• The absence of bacterial contamination (e.g. lipoproteins and endotoxins) has been confirmed using HEK-Blue™ TLR2 and HEK-Blue™ TLR4 cells.

Contents

Anti-HER2-Tra-hIgG4 (S228P) purified monoclonal antibody is provided azide-free and lyophilized. It is available in two quantities:

• her2tra-mab14: 100 µg
• her2tra-mab14-03: 3 x 100 µg

Product is shipped at room temperature

 Upon receipt, store at -20°C.

Citations