Triple-Specific Nanobody TriTE for Tumor Control and Side Effect Reduction
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Solution Overview
Problem
Current cancer treatments, including immunotherapy, are often ineffective and associated with strong side effects and immune-related disorders, with challenges in targeting and regulating immune cells effectively to combat tumors.
Innovation Solution
Development of an immunomodulation and anti-tumor-related nanobody that specifically binds to HLA-G, PD-L1, and CD3ε, forming a triple specific T-cell engager (TriTE) to activate and aggregate CD3-positive cells, promoting T cell proliferation and killing tumor cells, and can be administered directly for large-scale treatment.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional cancer treatments (surgery, radiation, chemotherapy, target therapy) are used, then tumors can be removed or controlled, but strong side effects and immune-related disorders occur
Solution Approach 1:
The patent segments the immune system's anti-tumor function into specific target components (PD-L1, HLA-G, CD3ε) and develops nanobodies that specifically target each component. This segmentation allows precise modulation of immune responses without the broad, non-specific damage caused by conventional chemotherapy and radiation therapy, thereby reducing side effects while maintaining tumor control effectiveness.
Solution Approach 2:
The patent introduces nanobodies as intermediary molecules that mediate between tumor cells and immune cells. These nanobodies specifically bind to PD-L1 on tumor cells and HLA-G on immune cells, acting as a bridge to restore immune recognition of tumors without directly damaging healthy tissues like conventional therapies, thus reducing harmful side effects while achieving tumor control.
2Reliability
If current immunotherapy methods are used, then anti-cancer ability is enhanced, but ineffectiveness and strong side effects persist
Solution Approach 1:
The patent applies local quality by designing nanobodies with specific binding properties for different targets at different locations. The nanobody against PD-L1 specifically binds to tumor cell surfaces, while the nanobody against HLA-G specifically binds to immune cell surfaces. This localized, specific binding enhances anti-cancer ability at the tumor site without causing systemic immune activation and side effects throughout the body, thereby improving treatment effectiveness.
Solution Approach 2:
The patent creates a composite immunotherapy approach by combining multiple nanobodies with different specificities (anti-PD-L1, anti-HLA-G, anti-CD3ε) into a coordinated therapy regimen. This composite strategy synergistically enhances anti-cancer ability by simultaneously blocking immune suppression mechanisms and activating T cells, while the specificity of each nanobody component prevents the strong side effects associated with non-specific immunotherapy methods.
3Reliability
If HLA-G and PD-L1 are targeted to suppress immune cells, then tumor growth is inhibited, but immune function regulation becomes complex
Solution Approach 1:
The patent extracts and isolates the specific molecular mechanisms (PD-L1 and HLA-G interactions) that mediate immune suppression in tumor microenvironments. By developing nanobodies that specifically target these extracted molecular targets, the complex immune function regulation is simplified into discrete, targetable molecular interactions, making the regulation more controllable and less complex while maintaining effective tumor growth inhibition.
4Reliability
If CD3ε is targeted for T cell activation, then immune function is enhanced, but specificity in tumor targeting is reduced
Solution Approach 1:
The patent merges multiple targeting strategies by combining nanobodies with different specificities (anti-PD-L1 for tumor targeting, anti-HLA-G for immune cell targeting, and anti-CD3ε for T cell activation) into a unified therapy approach. This merging ensures that CD3ε-mediated T cell activation is coupled with specific tumor and immune cell targeting through the other nanobodies, thereby maintaining both immune function enhancement and tumor targeting specificity simultaneously.
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 nanobody effectively binds to tumor cells, enhances T cell activation, and inhibits cancer cell growth, offering a novel approach to treating lung adenocarcinoma, breast cancer, glioblastoma, ovarian carcinoma, and oral cancer with improved efficacy compared to conventional antibodies.
Implementation Method 1
The present invention provides an immunomodulation and anti-tumor-related nanobody that specifically binds to a human leukocyte antigen-G (HLA-G), programmed cell death ligand 1 (PD-L1) and CD3 ε (CD3 epsilon)
Data Source
AI summary
The present disclosure provides an immunomodulation and anti-tumor-related nanobody that specifically binds to a human leukocyte antigen-G, a programmed cell death ligand 1, and CD3 ε. The present disclosure also provides the nucleic acid sequence of the immunomodulation and anti-tumor-related nanobody, and use of the immunomodulation and anti-tumor-related nanobody for treating cancer and immune-related disorders.