Anti-hPD1-Pem-hIgA2 features the constant region of the human IgA2 isotype and the variable region of pembrolizumab. Pembrolizumab is a humanized IgG4 monoclonal antibody that contains an engineered hinge region mutation (S228P) designed to prevent exchange of IgG4 molecules. This antibody targets the PD-1 receptor found on activated T cells, B cells, and myeloid cells. Under normal physiological conditions, PD-1 negatively regulates T cell activation thereby preventing autoimmunity [1]. Under pathological conditions, cancer cells produce PD-L1 (programmed cell death 1 ligand 1), the agonist that binds and activates PD-1. Activated PD-1 enables the cancer cells to evade the immune system. Pembrolizumab binds and blocks the activation of the PD-1 receptor, thereby resulting in the activation of T cells [2]. Pembrolizumab has been approved by the FDA for the treatment of metastatic malignant melanoma, and is currently under regulatory review in the EU [3].
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-hPD1-Pem-hIgA2 was generated by recombinant DNA technology. It has been produced in CHO cells and purified by affinity chromatography.
References:
- McDermott D. & Atkins M. 2013. PD-1 as a potential target in cancer therapy. Cancer Med. 2(5): 662–673.
- Tumeh PC. et al., 2014. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature. 515(7528):568-71.
- Poole RM., 2014. Pembrolizumab: first global approval. Drugs. 4(16):1973-81.
