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Anti-hVISTA isotype family

Blockade of VISTA with Anti-hVISTA mAbs
Blockade of VISTA with Anti-hVISTA mAbs

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) [1]. VISTA is predominantly expressed on antigen-presenting cells (APCs), and directly suppresses T cell proliferation and cytokine production [2]. Additionally, VISTA is expressed on a number of subsets of T cells (i.e. CD4+ and CD8+ cells) [3]. 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 [4].

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 [3]. 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 [5]. In addition, the IL-23/IL-17 inflammatory axis has been shown to regulate the inflammatory response within the TME [5]. 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.

 

References:

1. Lines, J.L. et al. 2014. VISTA is a novel broad-spectrum negative checkpoint regulator for cancer immunotherapy. Cancer Immunol Res 2, 510-517.
2. Lines, J.L. et al. 2014. VISTA is an immune checkpoint molecule for human T cells. Cancer Res 74, 1924-1932.
3. Nowak, E.C. et al. 2017. Immunoregulatory functions of VISTA. Immunol Rev 276, 66-79.
4. 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.
5. Li, N. et al. 2017. Immune-checkpoint protein VISTA critically regulates the IL-23/IL-17 inflammatory axis. Sci Rep 7, 148.

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