Vista modulators for diagnosis and treatment of cancer

Abstract

The present disclosure relates to compositions and therapeutic methods for activating an immune response in a patient in need thereof. In a preferred embodiment, the subject methods and compositions are able to antagonize the activity of VISTA, a naturally occurring “checkpoint” protein which contributes to immune tolerance, optionally in combination with an antagonist of a second checkpoint pathway such as PD-1. For example, such methods and compositions may be suitable for preventing and treating colon cancer or another cancer. An exemplary VISTA antagonist, specifically, an anti-VISTA antibody, is demonstrated herein to activate an immune response against cancer cells in vitro and in vivo, thereby conferring protective anti-tumor immunity which decreased tumor burden. Additionally, an additive benefit was observed when a VISTA antagonist was used in combination with a second checkpoint protein antagonist, specifically, an antibody against PD-1 ligand (PD-L1).

1 . A method for treating a subject having a condition that would benefit from upregulation of an immune response comprising: administering a VISTA antagonist, thereby inhibiting the VISTA-mediated suppression of immune responses, such that a condition that would benefit from upregulation of an immune response is treated. 
     
     
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