Anti-hCTLA4-hIgG1NQ

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

Anti-hCTLA4-hIgG1NQ features a mutated 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, it 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, it 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. It is undergoing clinical trials for lung cancer [4].

Anti-hCD20-hIgG1fut contains a N-glycosylation mutation of the constant region of the human IgG1 where potential asparagine (N) glycosylation sites are substituted by glutamine (Q) residues resulting in the production of a nonglycosylated antibody. Glycosylation of an antibody has no effect on antigen binding but is essential for Fc receptor-mediated activity [5]. In non-glycosylated antibodies the effector mechanisms mediated through the Fc receptors types (FcγRI, FcγRII, FcγRIII) and the C1q component of complement are severely compromised or ablated [6]. This antibody has been produced in CHO cells and purified by affinity chromatography with protein G.

Applications:   Anti-hCTLA4-hIgG1NQ can be used with Anti-hCTLA4-hIgG1 to study the impact of effector functions.

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. 25:166-72.
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 non-small cell lung cancer. Ther Adv Med Oncol. 4: 43–50.
Arnold J. et al., 2007. The impact of glycosylation on the biological function and structure of human immunoglobulins. Annu Rev Immunol 25:21-50.
Jefferis R., 2009. Glycosylation as a strategy to improve antibody-based therapeutics. Nat Rev Drug Discov. 8:226-34.