VISTA Blockade Enhances Anti-Tumor Immunity
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Solution Overview
Problem
Current cancer immunotherapies targeting immune checkpoint proteins like CTLA-4 and PD-1 have shown limited responses in clinical trials, highlighting the need for novel checkpoint proteins that can synergize with existing pathways to enhance anti-tumor immunity.
Innovation Solution
The identification and targeting of VISTA, a novel immune checkpoint protein, which when blocked, reverses the suppressive character of the tumor microenvironment, thereby promoting protective anti-tumor immunity by inhibiting VISTA-mediated immune suppression.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current cancer immunotherapies targeting CTLA-4 and PD-1 are used, then anti-tumor immune response is activated, but the response is limited and does not achieve sufficient therapeutic efficacy
Solution Approach 1:
The patent combines blockade of multiple immune checkpoint pathways (CTLA-4, PD-1/PD-L1, and VISTA) into a single therapeutic strategy. By simultaneously targeting these pathways with combination therapy, the patent achieves synergistic enhancement of anti-tumor immune responses that exceeds the efficacy of single-agent therapies, thereby resolving the limitation of modest response rates observed with current monotherapies
2Reliability
If VISTA blockade is implemented to reverse tumor microenvironment suppression, then protective anti-tumor immunity is enhanced, but the mechanism of immune suppression must be overcome
Solution Approach 1:
The patent applies preliminary anti-action by blocking VISTA and other checkpoint pathways before the immunosuppressive mechanisms can fully inhibit anti-tumor immunity. By preemptively preventing the binding interactions between checkpoint ligands and receptors, the patent reverses the suppressive character of the tumor microenvironment and enables effective anti-tumor immune responses to develop
Data Source
AI summary
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).