CLPTM1-Derived Peptides Targeting TGF-beta Signaling
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Solution Overview
Problem
Current therapies fail to effectively inhibit the immunosuppressive effects of transforming growth factor-beta (TGF-β), particularly in conditions associated with elevated TGF-β levels, as existing strategies often have pleiotropic effects and side impacts due to the protein's diverse roles in cell differentiation, development, and immune regulation.
Innovation Solution
Development of peptides derived from the extracellular domain of the Cleft Lip and Palate Transmembrane protein 1 (CLPTM1) receptor, which act as decoy receptors to bind and inhibit TGF-β, preventing its interaction with the CLPTM1 receptor, thereby reducing TGF-β's immunosuppressive effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing strategies to inhibit TGF-β are used, then TGF-β activity is reduced, but pleiotropic effects and side impacts occur due to the protein's diverse roles
Solution Approach 1:
The patent applies local quality by developing peptides that specifically target the CLPTM1 receptor-TGF-β interaction pathway. These peptides are designed to interfere only with the binding of TGF-β to its specific receptor complex (CLPTM1 + TGFBRs), rather than broadly inhibiting all TGF-β signaling. This localized approach allows selective inhibition of pathological TGF-β activity while preserving other physiological functions mediated through different TGF-β receptors or pathways, thereby reducing pleiotropic side effects.
2Adaptability or versatility
If broad TGF-β inhibition is achieved, then multiple TGF-β mediated processes are affected, but specificity and reduced side effects are compromised
Solution Approach 1:
The patent employs an intermediary approach by using peptides that act as blocking agents between TGF-β and its receptor complex. These peptides specifically block the interaction between TGF-β and the CLPTM1 receptor, serving as a targeted intermediary that prevents pathological signaling without affecting other TGF-β mediated processes. This allows versatile inhibition coverage for conditions driven by the CLPTM1-TGF-β pathway while maintaining high targeting specificity.
3Reliability
If TGF-β binding to CLPTM1 receptor is blocked, then immunosuppressive effects are reduced, but broader TGF-β signaling pathways may remain unaffected
Solution Approach 1:
The patent applies segmentation by focusing inhibition on a specific segment of the TGF-β signaling network - the CLPTM1 receptor binding interface. Rather than attempting to block all TGF-β signaling pathways simultaneously, the peptides are designed to specifically segment and block only the CLPTM1-mediated pathway. This segmented approach allows therapeutic reduction of immunosuppressive effects while leaving other TGF-β signaling segments (such as those mediated by alternative receptors) potentially intact, enabling more precise control over unwanted activity.
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 peptides specifically target TGF-β, reducing its immunosuppressive effects and minimizing side impacts by blocking TGF-β's interaction with the CLPTM1 receptor, offering a novel therapeutic approach for conditions characterized by elevated TGF-β levels, such as cancer and fibrotic diseases.
Implementation Method 1
peptides derived from the extracellular domain of the Cleft Lip and Palate Transmembrane protein 1 (CLPTM1) receptor, which act as decoy receptors to bind and inhibit TGF-β
Data Source
AI summary
The invention relates to apolypeptide capable of binding to TGF-β for use in treating or preventing a condition associated with elevated or unwanted levels of TGF-β, wherein said polypeptide is capable of inhibiting the interaction of TGF-β with the receptor CLPTM1.