Anti-VISTA Antibodies for Tumor Immune Checkpoint Blockade
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Solution Overview
Problem
Cancer cells and immune cells in the tumor microenvironment suppress the host's immune response, necessitating the development of therapeutic agents that inhibit negative immune checkpoint regulators to enhance anti-tumor immune responses.
Innovation Solution
Development of antibodies and antibody fragments that bind to V-domain Ig Suppressor of T cell Activation (VISTA), modulating or enhancing immune responses by targeting VISTA expressed on hematopoietic cells and in the tumor microenvironment, including specific CDR sequences and combinations with cytotoxic molecules.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If VISTA is expressed on hematopoietic cells in the tumor microenvironment, then immune suppression occurs, but blocking VISTA requires developing specific therapeutic antibodies
Solution Approach 1:
The patent introduces anti-VISTA antibodies as intermediary molecules that bind to VISTA on hematopoietic cells, blocking the immune suppression pathway. These antibodies act as mediators between the therapeutic goal (enhancing anti-tumor immunity) and the target (VISTA checkpoint regulator), thereby resolving the contradiction by providing a reliable mechanism to overcome immune suppression without requiring direct manipulation of complex cellular interactions
Solution Approach 2:
The patent employs parameter changes by developing antibodies with specific binding affinities and characteristics tailored to counteract VISTA-mediated suppression. By optimizing antibody parameters such as binding strength, specificity, and effector functions, the therapy reliably enhances anti-tumor immune responses while managing the complexity of therapeutic agent development
2Reliability
If antibodies bind to VISTA to modulate immune response, then anti-tumor immunity is enhanced, but specific binding to VISTA requires precise antibody design
Solution Approach 1:
The patent applies local quality by designing antibodies with precisely engineered complementarity-determining regions (CDRs) that target specific epitopes on VISTA. The CDR sequences are optimized to bind locally to particular regions of VISTA, ensuring high specificity and reliable immune modulation while managing the precision requirements of antibody manufacturing through focused optimization of key binding regions
Solution Approach 2:
The patent uses copying by creating multiple antibody variants with identical or similar CDR sequences that bind to VISTA. These replicated antibody designs with consistent binding specificities enable reliable immune response modulation while simplifying manufacturing precision requirements through standardized, reproducible antibody sequences
Data Source
AI summary
The present invention relates to novel antibodies and fragments that bind to a V-domain Ig Suppressor of T cell Activation (VISTA), and methods of making and using same. Methods of use include methods of treatment of cancer, including leukemias, lymphomas, solid tumors and melanomas.