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

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.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Mehta N,Maddineni S,Kelly RL,Lee RB,Hunter SA,Silberstein JL,Parra Sperberg RA,Miller CL,Rabe A,Labanieh L,Cochran JR

doi

10.1038/s41598-020-71519-4

subject

Has Abstract

pub_date

2020-09-16 00:00:00

pages

15171

issue

1

issn

2045-2322

pii

10.1038/s41598-020-71519-4

journal_volume

10

pub_type

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