High-Affinity TIGIT Antibody for Blocking CD155 Immunosuppression
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current immune checkpoint therapies, such as PD-1/L1 and CTLA-4 blockade, have limited efficacy in treating malignant tumors, with only 10-30% of patients responding effectively, and many developing secondary drug resistance, necessitating the development of antibodies targeting TIGIT to overcome immunosuppression and inhibit tumor growth.
Innovation Solution
A high-affinity TIGIT antibody is developed with specific CDR sequences (SEQ ID NO: 1-6) to block TIGIT binding to CD155, relieving immunosuppression and promoting anti-tumor immune cell function, potentially overcoming secondary drug resistance.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If PD-1/L1 or CTLA-4 blockade therapy is used, then anti-tumor ability is restored in some patients, but response rate is limited (only 10-30% long-lasting response) and secondary drug resistance develops
Solution Approach 1:
The patent segments the immune checkpoint therapy approach by targeting multiple independent checkpoints (TIGIT, PD-1, PD-L1, CTLA-4) rather than relying on a single checkpoint blockage. This segmentation allows the therapy to work through different mechanisms in different patients, addressing the limited response rate and secondary resistance issues of single-target therapies.
Solution Approach 2:
The patent creates a universal therapeutic strategy by developing TIGIT antibodies that can be used across multiple patient populations and tumor types. The antibody design incorporates humanized sequences and multiple isotypes (IgG1, IgG2, IgG4) to achieve broad applicability and overcome the adaptability limitations of checkpoint-specific therapies.
2Ease of operation
If single type of immune checkpoint therapy is applied, then treatment simplicity is maintained, but heterogeneity in receptor expression prevents effective treatment for majority of patients
Solution Approach 1:
The patent applies parameter changes by optimizing the antibody's binding affinity and specificity parameters to target TIGIT with high precision. The CDR sequences and framework regions are carefully designed to ensure consistent recognition of TIGIT across different patient populations, maintaining treatment simplicity while improving efficacy through precise molecular targeting.
3Measurement precision
If TIGIT antibody with high affinity is developed, then binding specificity is improved, but manufacturing complexity increases
Solution Approach 1:
The patent uses copying by employing humanized antibody sequences that replicate successful human immune responses. The CDR sequences are derived from human germinal center B cells, and the framework regions use human constant domains, simplifying manufacturing by avoiding complex chimeric structures while achieving high binding affinity through human-like epitope recognition.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The TIGIT antibody enhances anti-tumor immune responses, inhibiting tumor growth and metastasis, and prevents secondary drug resistance with improved specificity and safety at lower dosages.
Implementation Method 1
the antibody provided by the present disclosure relieves TIGIT-mediated immunosuppression and promotes the anti-tumor function of immune cells
Data Source
AI summary
The application provides an anti-TIGIT antibody or an antigen-binding fragment thereof, and a use thereof. The anti-TIGIT antibody or the antigen-binding fragment thereof comprises heavy chain variable regions CDR1, CDR2 and CDR3 with sequences as set forth in SEQ ID NOs: 1, 2 and 3; and light chain variable regions CDR1, CDR2 and CDR3 with sequences as set forth in SEQ ID NOs: 4, 5 and 6.