2. Academic Validation
  3. An engineered antibody binds a distinct epitope and is a potent inhibitor of murine and human VISTA

An engineered antibody binds a distinct epitope and is a potent inhibitor of murine and human VISTA

  • Sci Rep. 2020 Sep 16;10(1):15171. doi: 10.1038/s41598-020-71519-4.
Nishant Mehta 1,  Sainiteesh Maddineni 1,  Ryan L Kelly 2,  Robert B Lee 3,  Sean A Hunter 1 4,  John L Silberstein 1 5,  R Andres Parra Sperberg 1,  Caitlyn L Miller 1,  Amanda Rabe 1 4,  Louai Labanieh 1,  Jennifer R Cochran 6 7 8 9 10
Affiliations

Affiliations

  • 1 Department of Bioengineering, Stanford University, Stanford, CA, 94305, USA.
  • 2 xCella Biosciences, Menlo Park, CA, 94025, USA.
  • 3 Department of Chemical Engineering, Stanford University, Stanford, CA, 94305, USA.
  • 4 Cancer Biology Program, Stanford University School of Medicine, Stanford, CA, 94305, USA.
  • 5 Immunology Program, Stanford University School of Medicine, Stanford, CA, 94305, USA.
  • 6 Department of Bioengineering, Stanford University, Stanford, CA, 94305, USA. jennifer.cochran@stanford.edu.
  • 7 xCella Biosciences, Menlo Park, CA, 94025, USA. jennifer.cochran@stanford.edu.
  • 8 Department of Chemical Engineering, Stanford University, Stanford, CA, 94305, USA. jennifer.cochran@stanford.edu.
  • 9 Cancer Biology Program, Stanford University School of Medicine, Stanford, CA, 94305, USA. jennifer.cochran@stanford.edu.
  • 10 Immunology Program, Stanford University School of Medicine, Stanford, CA, 94305, USA. jennifer.cochran@stanford.edu.
PMID: 32938950 DOI: 10.1038/s41598-020-71519-4
Abstract

V-domain immunoglobulin (Ig) suppressor of T cell activation (VISTA) is an immune checkpoint that maintains peripheral T cell quiescence and inhibits anti-tumor immune responses. VISTA functions by dampening the interaction between myeloid cells and T cells, orthogonal to PD-1 and Other checkpoints of the tumor-T cell signaling axis. Here, we report the use of yeast surface display to engineer an anti-VISTA antibody that binds with high affinity to mouse, human, and cynomolgus monkey VISTA. Our anti-VISTA antibody (SG7) inhibits VISTA function and blocks purported interactions with both PSGL-1 and VSIG3 proteins. SG7 binds a unique epitope on the surface of VISTA, which partially overlaps with Other clinically relevant antibodies. As a monotherapy, and to a greater extent as a combination with anti-PD1, SG7 slows tumor growth in multiple syngeneic mouse models. SG7 is a promising clinical candidate that can be tested in fully immunocompetent mouse models and its binding epitope can be used for future campaigns to develop species cross-reactive inhibitors of VISTA.

Figures
Products