Anti-TIGIT Antibody Constructs for Immune Response Modulation
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Solution Overview
Problem
Current cancer immunotherapy approaches are limited in effectively modulating immune responses against tumour cells due to the inhibitory role of TIGIT, a protein that suppresses immune activation, necessitating the development of targeted therapeutic agents to antagonize TIGIT signaling.
Innovation Solution
The development of anti-TIGIT constructs comprising specific antibody moieties with defined heavy and light chain complementarity-determining regions (CDRs) that specifically bind to TIGIT, competing for its binding epitope and modulating its activity to enhance immune response against cancer cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If TIGIT signaling is left unmodulated, then immune suppression is maintained, but immune response against tumour cells is insufficient
Solution Approach 1:
The patent converts the harmful immune suppression caused by TIGIT into a beneficial immune response by developing antibody constructs that specifically bind to TIGIT and block its inhibitory signaling. The anti-TIGIT constructs (full-length antibodies, fragments, fusion proteins) antagonize TIGIT's suppressive function, transforming the immunosuppressive pathway into an immunostimulatory one that enhances tumour cell recognition and destruction.
2Adaptability or versatility
If conventional immunotherapy approaches are used, then general immune activation is achieved, but targeted modulation of TIGIT signaling is insufficient
Solution Approach 1:
The patent applies local quality by designing antibody constructs with specific variable regions (VH and VL domains with defined CDRs) that are tailored to bind specifically to TIGIT. This localized specificity ensures that the immunomodulatory effect is precisely targeted at TIGIT-expressing cells rather than causing general immune activation, providing both adaptability and reliability in TIGIT signaling modulation.
Solution Approach 2:
The patent employs parameter changes by modifying antibody constructs in various formats (full-length antibodies, fragments like scFv and Fab, fusion proteins with Fc domains) to optimize their binding affinity and functional activity against TIGIT. These parameter modifications enhance the reliability of TIGIT signaling antagonism while maintaining versatility in immune response modulation.
3Productivity
If broad-spectrum immunotherapy is applied, then general immune activation occurs, but specific TIGIT-mediated suppression is not effectively overcome
Solution Approach 1:
The patent introduces anti-TIGIT antibody constructs as intermediaries that specifically bind to TIGIT on regulatory T cells and other immune cells, blocking the interaction between TIGIT and its ligands (such as PD-L1). This intermediary action directly counteracts TIGIT-mediated suppression while maintaining broad immune cell activation, thereby overcoming the contradiction between productivity and harmful suppression.
Data Source
AI summary
The present application provides anti-TIGIT constructs that bind to TIGIT (e.g., anti-TIGIT antibodies), nucleic acid molecules encoding an amino acid sequence of the anti-TIGIT, vectors comprising the nucleic acid molecules, host cells containing the vectors, methods of preparing the anti-TIGIT construct, pharmaceutical compositions containing the anti-TIGIT construct, and methods of using the anti-TIGIT construct or compositions.