VISTA-Ig Fusion Protein Modulates T Cell Activity
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Solution Overview
Problem
Current treatments for autoimmune disorders and inflammatory conditions often rely on immunosuppressive medications that can have severe side effects, and there is a need for a novel molecule that can modulate T cell activity to effectively manage these conditions.
Innovation Solution
Development of a VISTA fusion protein comprising a polypeptide with at least 90% sequence identity to the extracellular domain of VISTA, combined with an immunoglobulin protein, which can be administered systemically to regulate immune responses and treat autoimmune disorders and inflammatory conditions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional immunosuppressive medications are used to treat autoimmune disorders and inflammatory conditions, then immune response is suppressed, but severe side effects occur
Solution Approach 1:
The VISTA fusion protein is designed to act specifically on T cells through the VISTA domain, which binds to PD-1 receptors on T cells to modulate their activity. The immunoglobulin portion provides targeted delivery and extends circulation half-life. This localized, specific action on T cells allows for selective immune modulation without the broad suppression and severe side effects associated with traditional immunosuppressive medications that affect multiple immune cell types and pathways.
2Adaptability or versatility
If a novel molecule is developed to modulate T cell activity, then specific immune regulation is achieved, but treatment complexity increases
Solution Approach 1:
The VISTA fusion protein combines two functional elements into a single molecule: the VISTA domain (which modulates T cell activity by binding PD-1) and an immunoglobulin domain (which provides targeted delivery, extends half-life, and enables purification). This merging of functions into one molecule simplifies the treatment approach compared to using multiple separate agents, while maintaining specific immune regulation capability.
Solution Approach 2:
The immunoglobulin portion of the fusion protein serves multiple functions: it facilitates purification through affinity tags, extends the circulation half-life of the therapeutic molecule, enables targeted delivery to T cells, and provides a platform for potential conjugation with other therapeutic moieties. This multi-functionality reduces the need for additional separate components, thereby simplifying the overall treatment complexity.
Data Source
AI summary
The present invention relates to a fusion proteins comprising regulatory T cell protein, VISTA (V-domain Immunoglobulin Suppressor of T cell Activation (PD-L3) and an immunoglobulin protein (Ig). The invention also provides the use of VISTA polypeptides, multimeric VISTA polypeptides, VISTA-conjugates (e.g., VISTA-Ig), and VISTA antagonists for the treatment of autoimmune disease, allergy, and inflammatory conditions.