Anti-hVISTA isotype family
The Anti-hVISTA isotype family is a collection of recombinant monoclonal antibodies that feature a:
- Variable region that specifically targets human VISTA
- Constant region that is either a natural (IgG1) or engineered (IgG1NQ and IgG1fut) human IgG1 isotype
The different isotypes in this collection provide various effector functions (i.e. decreased ADCC). The Anti-hVISTA isotype family has been generated by recombinant DNA technology, produced in CHO cells, and purified by protein G affinity chromatography.
VISTA: the target
V-domain Ig-containing suppressor of T-cell activation (VISTA), also known as programmed death-1 homolog (PD-1H), is a distant member of the CD28/B7 protein superfamily, sharing homology with another important immune checkpoint, PD-L1 (programmed death receptor 1) . VISTA is predominantly expressed on antigen-presenting cells (APCs), and directly suppresses T cell proliferation and cytokine production . Additionally, VISTA is expressed on a number of subsets of T cells (i.e. CD4+ and CD8+ cells) . Thus, VISTA can be considered both a ligand and a receptor, whereby it transmits both extrinsic and intrinsic inhibitory signals to T cells. However, due to the lack of knowledge of its receptor, the molecular mechanism of how VISTA regulates effector T cell activation is not well understood .
VISTA in the context of cancer immunotherapy
VISTA has been found to be heightened on cells that infiltrate the tumor microenvironment (TME), and therefore VISTA blocking antibodies are of interest . They function to inhibit the engagement of VISTA with its unknown receptor on T cells or by directly targeting VISTA expressed on T cells, preventing VISTA from providing negative signaling. Differing from its closest relative, PD-L1, VISTA has not been found to be expressed on tumor cells and is, therefore, a promising target for immune checkpoint blockade therapy to boost the anti-tumor T cell response. Interesting, VISTA has also been shown to play a key role in the suppression of the IL-23/IL-17-mediated inflammatory axis by inhibiting the activation of dendritic cells and the production of IL-23 following TLR7 stimulation, as well as controlling IL-17 production by T cell subsets . In addition, the IL-23/IL-17 inflammatory axis has been shown to regulate the inflammatory response within the TME . Therefore, targeting VISTA could benefit the treatment of not only autoimmune and inflammatory diseases but also boost the response to cancer therapy. Taken all together, VISTA is a highly unique immune checkpoint that regulates both innate and adaptive immune responses.
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