Human VISTA Antibody - Onvatilimab IgG1NQ Isotype

Non-glycosylated human IgG1 monoclonal antibody (mAb) against human VISTA

Anti-hVISTA-hIgG1NQ is a recombinant monoclonal antibody (mAb) featuring a variable region that recognizes human VISTA, a member of the CD28/B7 protein superfamily, and a non-glycosylated constant region of the human IgG1 (hIgG1NQ) isotype.  

V-domain Ig-containing suppressor of T-cell activation (VISTA), also known as programmed death-1 homolog (PH-1H) is a known immune checkpoint, that directly suppresses T cell activation, proliferation, and cytokine production [1]. VISTA can be considered both a ligand and a receptor, whereby it transmits inhibitory signals to T cells, either extrinsically, through expression on myeloid cells (i.e. macrophage and dendritic cells) and binding to an unknown receptor on T cells, or intrinsically, through its expression on T cells (i.e. CD4+, CD8+) [2]. In the context of cancer immunotherapy, VISTA has been found to be heightened on cells that infiltrate the tumor microenvironment (TME) and not the tumor cells themselves, therefore, VISTA blocking antibodies are of interest. These function to inhibit the engagement of VISTA with its receptor on T cells or by directly targeting VISTA expressed on naïve and effector T cells, preventing it from providing negative signaling [1, 2].

Features of Anti-hVISTA-hIgG1NQ:

• Targets specifically human VISTA
• Features the hIgG1NQ constant region for abrogated effector function
• Functionally validated by flow cytometry

Anti-hVISTA-hIgG1NQ contains an N-glycosylation mutation in the constant region of human IgG1. Potential asparagine (N) glycosylation sites are substituted by glutamine (Q) residues, resulting in the production of a non-glycosylated antibody. Glycosylation of an antibody has no effect on antigen binding but is essential for Fc receptor-mediated activity, and therefore, the effector function of Anti‑hVISTA‑hIgG1NQ is severely compromised. Anti-hVISTA-hIgG1NQ was generated by recombinant DNA technology, produced in CHO cells, and purified by affinity chromatography with protein G.

References:

1. Nowak, E.C. et al. 2017. Immunoregulatory functions of VISTA. Immunol Rev 276, 66-79.
2. Xu, W. et al. 2018. The structure, expression, and multifaceted role of immune-checkpoint protein VISTA as a critical regulator of anti-tumor immunity, autoimmunity, and inflammation. Cell Mol Immunol 15, 438-446.