Fusion Protein Restoring Exhausted T Cell Function
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Solution Overview
Problem
Current treatments for cancer and chronic viral infections, such as those caused by HBV, face limitations due to side effects, drug resistance, and the inability to effectively restore the function of antigen-specific T cells, which are crucial for immune response.
Innovation Solution
A fusion protein is developed that recognizes and activates failing immune cells by combining immune checkpoint-specific antibodies with cytokines or their functional mutants, connected through a non-functional amino acid fragment to prevent protein folding interference, thereby enhancing immune cell function and numbers.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If checkpoint inhibitory antibodies are used to restore immune cell function, then the function of exhausted immune cells is restored, but the amount of immune cells does not increase and treatment efficacy is limited for patients lacking effector cells
Solution Approach 1:
The patent combines two functional components into a single fusion protein: (1) checkpoint inhibitory antibody component for restoring immune cell function, and (2) immune cell activating component for increasing immune cell numbers. This merging allows the single protein to simultaneously address both the functional restoration and quantity increase of immune cells, resolving the contradiction between these two parameters.
Solution Approach 2:
The fusion protein is designed with multi-functionality to perform multiple roles: it acts as both a checkpoint inhibitor (restoring function) and an immune cell activator (increasing numbers). This universal design allows a single therapeutic agent to address multiple aspects of immune cell failure, simultaneously improving reliability and quantity of immune cells.
2Reliability
If cytokines are used to activate immune cells, then immune cell function is enhanced, but side effects occur due to activation of non-target cells
Solution Approach 1:
The fusion protein employs local quality by combining a checkpoint inhibitory antibody component (which provides target-specific recognition) with a cytokine or activating ligand component. The antibody portion ensures that activation occurs only at the specific target site (exhausted immune cells expressing checkpoint receptors), while the cytokine/ligand portion provides the activating signal. This spatial and functional localization ensures that immune cell activation is directed specifically to target cells, minimizing activation of non-target cells and reducing side effects.
Solution Approach 2:
The checkpoint inhibitory antibody component acts as an intermediary that mediates between the cytokine/activating ligand and the target immune cells. It provides specific recognition and binding to exhausted immune cells, thereby directing the activating signal only to the intended target cells rather than diffusely activating all cells expressing cytokine receptors. This intermediary function ensures selective activation and reduces harmful side effects.
3Adaptability or versatility
If separate checkpoint inhibitory antibody and activating ligand are used, then each component can perform its function, but the treatment requires multiple components and has limited efficacy for patients lacking effector cells
Solution Approach 1:
The patent merges the checkpoint inhibitory antibody and the activating ligand (cytokine or ligand) into a single fusion protein molecule. This consolidation reduces the number of separate treatment components from two to one, simplifying the treatment regimen. The fusion protein maintains the functional capabilities of both components while eliminating the need for separate administration of multiple agents.
Solution Approach 2:
The fusion protein achieves multi-functionality by incorporating both checkpoint inhibition and immune cell activation capabilities within a single molecular entity. This universal design allows the single protein to provide comprehensive therapeutic coverage, addressing both functional restoration and cell quantity increase, while simplifying the treatment complexity compared to using separate agents.
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 fusion protein effectively restores the function of immune cells, increasing their numbers and enhancing the body's ability to inhibit tumor growth and control viral infections, offering a promising clinical solution with reduced side effects.
Implementation Method 1
the functional area for recognizing the failing immune cell
Implementation Method 2
the functional area for conducting activation and amplification on the failing immune cell uses cytokine or functionally-similar mutant, a ligand or functionally-similar mutant of the phenotypic receptor, or an activating antibody to activate and amplify the failing immune cells
Data Source
AI summary
A fusion protein for restoring functions of failing immune cells and application thereof. The fusion protein has a functional area for recognizing the failing immune cell and a functional area for conducting activation and amplification on the failing immune cell. The two functional areas are connected through a non-functional amino acid fragment with a certain length. The functional area for recognition uses the immune checkpoint specific antibody to recognize a phenotypic receptor of failing immune cells. The functional area for conducting activation and amplification adopts the cytokine or functionally-similar mutants, a ligand of the phenotypic receptor or functionally-similar mutants or an activating antibody to activate failing immune cells. The fusion protein recognizes failing immune cells, conducts activation and amplification on recognized failing immune cells, restores functions of killing antigen positive cells by the immune cells, and enhances inhibition of tumor growth and virus infection control.