Bispecific Agents Modulating CEACAM1 and TIM3 Interactions
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Solution Overview
Problem
Current treatments for T-cell tolerance-related immune disorders, such as cancer and autoimmune diseases, are inadequate, as existing methods fail to effectively modulate T-cell tolerance, leading to either excessive immune suppression or inadequate immune response.
Innovation Solution
The modulation of T-cell tolerance is achieved by enhancing or inhibiting the interactions between CEACAM1 and TIM3, using bispecific agents that bind to both molecules, thereby regulating their signaling and expression, allowing for the development of targeted therapies for autoimmune diseases and cancer.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing immune suppression methods are used to treat autoimmune diseases, then immune response is reduced, but T-cell tolerance cannot be effectively modulated leading to inadequate treatment
Solution Approach 1:
The patent changes the molecular parameters by targeting specific ligand-receptor interactions (CEACAM1-Galectin-9 and TIM3-Galectin-9) rather than using non-specific immune suppression. This allows precise modulation of T-cell tolerance through blocking these specific interactions, thereby improving both the effectiveness and adaptability of the treatment.
2Reliability
If existing cancer treatments are used to enhance immune response, then immune activation occurs, but T-cell tolerance cannot be effectively abrogated leading to inadequate anti-tumor immunity
Solution Approach 1:
The patent changes the approach by specifically blocking the Galectin-9 binding to CEACAM1 and TIM3 receptors, which are critical for maintaining T-cell tolerance. This parameter change at the molecular interaction level enables effective abrogation of T-cell tolerance and enhances anti-tumor immunity without the limitations of existing treatments.
3Adaptability or versatility
If non-specific immune modulation is used, then general immune response is affected, but precise control of T-cell tolerance is lost
Solution Approach 1:
The patent introduces blocking agents that specifically intercept the Galectin-9 binding to CEACAM1 and TIM3 receptors. These intermediary molecules provide precise control over T-cell tolerance modulation by selectively blocking the specific ligand-receptor interactions without affecting other immune pathways, thereby maintaining both adaptability and measurement precision.
Data Source
Figure 1A~1B
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AI summary
Described herein are compositions and methods for the modulation of T-cell tolerance, which can be upregulated or down regulated by concurrent enhancement or inhibition of CEACAM1/TIM3 interactions. As described herein, the discovery that CEACAM1 is a direct ligand of TIM3 and vice versa has been shown in cis and in trans. In addition, as demonstrated herein, CEACAM1 and TIM3 are co-regulated during the course of T-cell activation.