Fc-Cd80 Fusion Protein C-Terminal Placement
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Solution Overview
Problem
Current cancer treatments using CD80 fusion proteins face limitations due to interference with binding abilities when placing CD80 molecules at the N-terminal, affecting their efficacy in targeting multiple tumor-related antigens and immune checkpoint molecules.
Innovation Solution
A CD80 fusion protein with the CD80 extracellular domain linked to an immunoglobulin Fc domain at the C-terminal, combined with a second effector molecule at the N-terminal, enhances binding affinity to CD28, CTLA-4, and PD-L1, and can be conjugated with various antibody fragments or receptor domains to improve tumor inhibition effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If CD80 molecules are placed at the N-terminal of fusion protein, then the binding ability to CD28, CTLA-4 and PD-L1 is maintained, but the binding capability is interfered with and reduced
Solution Approach 1:
The patent inverts the conventional N-terminal placement of CD80 to C-terminal placement in the Fc-CD80 fusion protein structure. This inversion resolves the technical contradiction by eliminating steric interference while maintaining binding ability, allowing the CD80 extracellular domain to effectively bind to CD28, CTLA-4, and PD-L1 without the positional constraints that limited previous designs.
2Adaptability or versatility
If CD80 fusion protein is used to target multiple tumor-related antigens, then the therapeutic potential is improved, but the interference with binding abilities occurs
Solution Approach 1:
The patent segments the fusion protein into distinct functional modules: the Fc domain provides structural stability and half-life extension, while the C-terminal CD80 extracellular domain provides targeted binding functionality. This segmentation allows each component to perform its specific function without interfering with the other, enabling the protein to target multiple antigens (CD28, CTLA-4, PD-L1) with reliable binding ability.
3Device complexity
If conventional CD80 fusion protein structure is used, then the structure is simple, but the efficacy in targeting multiple tumor-related antigens is limited
Solution Approach 1:
The patent creates a composite fusion protein structure combining the Fc domain (from immunoglobulin) with the CD80 extracellular domain. This composite structure leverages the advantageous properties of both components: the Fc domain contributes structural stability, extended half-life, and reduced immunogenicity, while the CD80 domain provides multifunctional binding capability to CD28, CTLA-4, and PD-L1, thereby enhancing overall tumor inhibition efficacy without excessive structural complexity.
Data Source
AI summary
A Fc-CD80 fusion protein has a CD80 extracellular domain (ECD) linked to a C-terminal of an immunoglobulin Fc domain. The Fc-CD80 fusion protein can be used for the preparation of a conjugate, the conjugate including the Fc-CD80 fusion protein as a first component, and a second component containing a second effector molecule, the second component being located at an N-terminal of the first component. In addition, a conjugate including the Fc-CD80 fusion protein, a pharmaceutical composition including the Fc-CD80 fusion protein and/or the conjugate are effective for the treatment or prevention of cancerous diseases in individuals.