Chimeric Protein Targeting TNF-Producing Cells
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current therapies for diseases involving excessive TNF activity, such as rheumatoid arthritis and cancer, often have limited efficacy as they primarily block TNF function rather than addressing the source of TNF production, leading to incomplete protection and potential side effects.
Innovation Solution
A chimeric protein comprising a cell-specific targeting agent, like the TNF binding protein, connected with Yersinia outer protein P (YopP) via a translocation polypeptide, allowing selective targeting and destruction of TNF-producing cells, thereby reducing TNF production and activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If anti-TNF antibodies or soluble TNF receptors are used to block TNF action, then TNF function is inhibited, but the source of TNF production remains active leading to incomplete protection and potential side effects
Solution Approach 1:
The invention extracts and eliminates the source of TNF production by selectively destroying TNF-producing cells, rather than merely blocking TNF function. This is achieved through chimeric proteins that specifically target and kill the cells producing excessive TNF, removing the ongoing source of pathology.
Solution Approach 2:
The invention uses chimeric proteins as intermediary agents that combine targeting specificity with cytotoxic activity. These chimeric molecules mediate between the diagnostic need for TNF identification and the therapeutic need for cell destruction, providing a bridge between detection and elimination of the pathogenic source.
2Duration of action of stationary object
If cytokine-producing cells are destroyed to prevent further cytokine synthesis, then durable protection is achieved, but systemic effects may occur
Solution Approach 1:
The invention applies local quality by making the cytotoxic agent highly specific to TNF-producing cells through the use of cell-specific targeting agents. This ensures that only the cells producing excessive TNF at specific disease sites are destroyed, while other cells throughout the body remain unaffected, thus achieving durable local protection without systemic damage.
Solution Approach 2:
The invention changes the parameter of cellular specificity by modifying the targeting mechanism to recognize unique surface markers on TNF-producing cells. This parameter change allows selective destruction of pathogenic cells while preserving normal cells, enabling durable therapy with minimized systemic effects.
3Reliability
If chimeric proteins are used to selectively target and destroy TNF-producing cells, then TNF production is reduced at specific sites, but the complexity of the therapeutic agent increases
Solution Approach 1:
The invention merges multiple functional components into a single chimeric protein molecule: a cell-specific targeting agent for recognition, a translocation domain for cellular entry, and a cytotoxic effector domain for cell killing. This consolidation achieves selective targeting and destruction in one agent, balancing enhanced efficacy with manageable complexity through functional integration.
Solution Approach 2:
The chimeric protein structure embodies multi-functionality by incorporating domains that perform targeting, translocation, and cytotoxic activities within a single molecule. This universal design allows one agent to accomplish multiple therapeutic tasks, reducing the need for separate diagnostic and therapeutic components.
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
This approach provides more durable protection by selectively targeting and reducing TNF production at specific sites, minimizing systemic effects and enhancing therapeutic outcomes in diseases like rheumatoid arthritis and cancer.
Implementation Method 1
connected by a translocation polypeptide, wherein the translocation polypeptide enables the chimeric protein or a fragment thereof to be translocated from the endosome to the cytosol of a target cell
Implementation Method 2
YopP, which has reduced or non-apoptotic activity
Implementation Method 3
YopP seems to be a protease, possibly of the de-SUMOylating family... Mutations in catalytic triad (His 109, Glu 128 and Cys 172 in YopP) disable YopP to inhibit either the MAPK or the NF-kB pathway
Data Source
AI summary
The present invention relates to a chimeric protein comprising a cell-targeting agent and a Yersinia outer protein, connected by a translocating polypeptide. The invention further relates to the preparation and use of such chimeric protein.