Peptide Superagonists for CD8 Treg Modulation
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Solution Overview
Problem
Current methods are inadequate in effectively mobilizing or depleting CD8 T regulatory cells (CD8 Treg) to treat autoimmune disorders and cancer, as they fail to specifically target and modulate CD8 Treg activity, leading to insufficient immune regulation and potential immune suppression.
Innovation Solution
Development of peptide superagonists and antibodies that bind to CD8 Treg cells, specifically targeting T cell receptors (TCRs) and MHC class Ib molecules to mobilize or deplete CD8 Treg cells, thereby regulating CD4 T cell activity and immune responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current methods are used to treat autoimmune disorders and cancer, then general immune suppression or activation occurs, but specific modulation of CD8 Treg activity is insufficient
Solution Approach 1:
The patent employs peptide superagonists as intermediary molecules that specifically bind to MHC class Ib molecules on CD4 T cells, thereby recruiting and activating CD8 Treg cells through their T cell receptors. This intermediary approach enables precise targeting of CD8 Tregs without requiring direct manipulation of the cells themselves, resolving the contradiction between achieving specific modulation and maintaining ease of therapy development
Solution Approach 2:
The invention modifies peptide sequences to create superagonists with enhanced binding affinity to MHC class Ib molecules compared to native peptides. By changing specific amino acid parameters in the peptide structure, the patent achieves significantly improved ability to mobilize CD8 Tregs, thereby increasing the reliability and specificity of CD8 Treg modulation while building upon existing peptide-based approaches
2Object-affected harmful factors
If CD8 Treg cells are mobilized to suppress autoimmune responses, then autoimmunity and allograft rejection are reduced, but anti-tumor immune responses may be insufficient
Solution Approach 1:
The patent applies the same CD8 Treg mobilization strategy using peptide superagonists to opposite therapeutic goals: suppressing autoimmune responses in autoimmune diseases and enhancing anti-tumor immunity in cancer. By inverting the desired outcome while maintaining the core mechanism, the invention demonstrates adaptability across different disease conditions - mobilizing CD8 Tregs to suppress pathogenic CD4 responses in autoimmunity, while depleting them to unleash anti-tumor CD4 responses in cancer therapy
3Productivity
If antibodies are used to deplete CD8 Treg cells for cancer treatment, then anti-tumor immune responses are enhanced, but immune regulation is compromised
Solution Approach 1:
The patent employs Fc-engineered antibodies as intermediaries that specifically bind to CD8 Treg cells and recruit immune effector mechanisms for selective depletion. The engineered Fc regions enhance binding to Fc gamma receptors on immune cells, enabling precise targeting and depletion of CD8 Tregs in the tumor microenvironment while preserving immune regulation in healthy tissues through controlled antibody distribution and clearance
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 approach effectively mobilizes or depletes CD8 Treg cells, reducing antibody-mediated rejection and autoimmunity while enhancing anti-tumor immune responses, providing a targeted strategy for immune regulation.
Implementation Method 1
Peptide superagonists for CD8 Treg... binds to a T cell receptor (TCR) on the CD8 Treg cell and to an MHC class Ib molecule on a CD4 T cell
Implementation Method 2
Antibodies that can deplete Treg cells... bind to unique molecules on CD8 Treg cells, including T cell receptors (TCRs)
Data Source
AI summary
Aspects of the invention are drawn to compositions and methods for modulating CD8 Treg mobilization in the treatment of autoimmune disorders, rejection of transplanted organs and cancer.