Anti-hCTLA4-hIgG1fut

Non-fucosylated monoclonal human IgG1 antibody against human CTLA-4

Anti-hCTLA4-hIgG1fut features the constant region of the human IgG1 isotype and the variable region of ipilimumab. Ipilimumab is a fully human IgG1 monoclonal antibody that targets CTLA-4 (also known as CD152), a negative regulator of T cell activation. By binding CTLA-4, ipilimumab inhibits negative signals that physiologically downregulate T cell activation and exerts its therapeutic activity by upregulating the antitumor activity of T lymphocytes [1,2].

In addition, Ipilimumab induces antibody-dependent cell-mediated cytotoxicity (ADCC) and TNF-α production [3]. Ipilimumab has been approved by the FDA for the treatment of unresectable or metastatic melanoma. Ipilimumab is undergoing clinical trials for other types of cancers, including lung cancer [4].

Anti-hCTLA4-hIgG1fut is a non-fucosylated antibody. The absence of the fucose residue from the N-glycans of IgG-Fc results in dramatic enhancement of antibody-dependent cellular cytotoxicity (ADCC) without any detectable change in complement-dependent cytotoxicity (CDC) or antigen binding capability [5,6].

Anti-hCTLA4-hIgG1fut was generated by recombinant DNA technology. It has been produced in CHO cells that are deficient for fucosylation and purified by affinity chromatography with protein G.

References:

Grosso JF. & Jure-Kunkel MN., 2013. CTLA-4 blockade in tumor models: an overview of preclinical and translational research. Cancer Immun. 13:5.
Maio M. et al., 2013. Update on the role of ipilimumab in melanoma and first data on new combination therapies. Curr Opin Oncol. 25(2):166-72.
Laurent S.. et al., 2013. The engagement of CTLA-4 on primary melanoma cell lines induces antibody-dependent cellular cytotoxicity and TNF-α production. J Transl Med. 11:108.
Tomasini P., 2012. Ipilimumab: its potential in nonsmall cell lung cancer. Ther Adv Med Oncol. 4(2): 43–50.
Yamane-Ohnuki N. & Satoh M., 2009. Production of therapeutic antibodies with controlled fucosylation.corresponding MAbs. 1(3): 230–236.
Mizushima T., 2011. Structural basis for improved efficacy of therapeutic antibodies on defucosylation of their Fc glycans. Genes Cells. 16(11): 1071–1080.

Figures

Comparison of ADCC potency for native and engineered anti-human CTLA-4 antibody isotypes: Raji-hCTLA4 cells were incubated with gradient concentrations of Anti-hCTLA4 or Anti-β-galactosidase (β-gal) mAbs for 1 hour. Jurkat-Lucia™ NFAT-CD16 effector cells were then co-incubated with targets 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 human CTLA-4

Clonality: Monoclonal antibody

Isotype: Human IgG1, kappa

Source: CHO cells

Purity: Purified by affinity chromatography with protein G

Quality control:

• Binding of Anti-hCTLA4-hIgG1fut to hCTLA4 has been validated 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

• 100 µg purified anti-hCTLA4-hIgG1fut antibody, provided azide-free and lyophilized

Product is shipped at room temperature.

Store lyophilized antibody  at -20 °C.

Lyophilized product is stable for at least 1 year.