Anti-hCTLA4-hIgA2 features the constant region of the human IgA2 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].
IgA2 is found predominantly in secretory lymphoid tissues, where it plays a critical role in mucosal immunity. IgA2 is highly resistant to enzymatic degradation by bacterial proteases, due to a short hinge region. IgA2 displays no complement dependent cytotoxicity (CDC) and low ADCC.
Anti-hCTLA4-hIgA2 was generated by recombinant DNA technology. It has been produced in CHO cells and purified by affinity chromatography with peptide M.
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.
