Activin Signaling Blockade to Reduce Treg-Mediated Tumor Immunosuppression
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Solution Overview
Problem
Immunosuppressive regulatory T cells (Treg) hinder effective anti-tumor immune responses and immunotherapies, necessitating new therapeutic strategies to modulate Treg function for cancer treatment.
Innovation Solution
Targeting Activin signaling with modulators, such as antibodies or small molecules, to inhibit Treg function and proliferation, combined with cell-based anti-tumor vaccines, to enhance immune responses against cancer cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If Treg function, activity, or proliferation is increased to maintain immune homeostasis, then immune tolerance is improved, but anti-tumor immune response is suppressed
Solution Approach 1:
The patent applies local quality by differentiating the treatment effect between tumor microenvironment and normal tissues. Activin signaling inhibition is targeted specifically to reduce Treg function in the tumor microenvironment where it causes immunosuppression, while maintaining Treg-mediated immune tolerance in normal tissues. This is achieved through localized delivery of Activin inhibitors to the tumor site, allowing selective modulation of Treg activity where it is harmful without compromising systemic immune homeostasis.
Solution Approach 2:
The patent employs parameter changes by modulating the activity state of Treg cells through Activin signaling inhibition. By changing the signaling parameters (Activin receptor activation levels) in the tumor microenvironment, the functional state of Treg cells is altered from immunosuppressive to immunocompetent, thereby enhancing anti-tumor immunity while preserving their homeostatic function in normal conditions.
2Object-affected harmful factors
If Activin signaling is inhibited to reduce Treg-mediated immune suppression, then anti-tumor immune response is enhanced, but tumor growth suppression may be reduced
Solution Approach 1:
The patent uses cell-based anti-tumor vaccines as an intermediary to bridge the gap between Activin signaling inhibition and effective anti-tumor immunity. The vaccines serve as a mediator that stimulates anti-tumor immune responses independently of Treg suppression, allowing the system to achieve both reduced immunosuppression and maintained tumor growth suppression through complementary mechanisms.
Solution Approach 2:
The patent merges two therapeutic approaches: Activin signaling inhibition and cell-based anti-tumor vaccination. By combining these treatments, the patent achieves synergistic effects where Activin inhibition reduces Treg-mediated immunosuppression while the vaccine provides direct anti-tumor immunity, together overcoming the trade-off between enhancing anti-tumor response and maintaining tumor growth suppression.
3Object-affected harmful factors
If Activin antagonists are administered to inhibit Treg proliferation, then Treg-mediated immune suppression is reduced, but treatment complexity increases
Solution Approach 1:
The patent applies universality by using Activin antagonists that can inhibit Treg proliferation across multiple cancer types and contexts. The same Activin inhibitor molecule serves multiple therapeutic functions: reducing Treg-mediated immunosuppression, enhancing adoptive cell therapy efficacy, and working across different cancer models, thereby simplifying the overall treatment approach despite the molecular complexity of the mechanism.
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
Reduces Treg-mediated immune suppression by 5-100% and decreases tumor size by 1-100%, improving the effectiveness of anti-tumor therapies.
Implementation Method 1
Targeting Activin signaling with modulators, such as antibodies or small molecules, to inhibit Treg function and proliferation
Data Source
AI summary
The present invention relates to compositions and methods for treating cancer by targeting the Activin signaling pathway. In certain embodiments, combining Activin blockade with immunomodulation alters regulatory T (Treg) cell-mediated immune regulation and treats cancer.