T1D T Cell Epitopes for Targeted Immune Tolerance
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Solution Overview
Problem
Current treatments for Type 1 Diabetes (T1D) are inadequate, leading to chronic complications and reduced life expectancy, with no disease-modifying therapies available, and there is a need for new treatments to manage the autoimmune destruction of pancreatic β cells.
Innovation Solution
Identification of immunoprevalent T cell epitopes associated with T1D, which are used to develop peptides and nucleic acids that induce immune tolerance by targeting CD8+ T cells, utilizing delivery agents and immunomodulators to present these epitopes on tolerogenic cells, thereby suppressing harmful T cell responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If standard insulin substitution therapy is used to manage T1D, then blood glucose levels can be controlled, but patients remain dependent on lifelong therapy with no cure and face chronic complications
Solution Approach 1:
The patent extracts and isolates specific T cell epitopes (such as Insulin B:9-23, GAD2:190-205, IA-2:610-626) from the complex autoimmune response in T1D. By identifying and targeting these specific epitopes with monoclonal antibodies or tolerance-inducing therapies, the treatment simplifies the complex autoimmune process into targetable molecular components, moving from managing symptoms to addressing the root cause of β cell destruction
Solution Approach 2:
The patent introduces monoclonal antibodies or epitope-specific tolerogenic therapies as intermediaries between the immune system and pancreatic β cells. These intermediaries specifically bind to pathogenic T cell epitopes, blocking their ability to destroy β cells while preserving normal insulin function. This mediator approach transforms the direct autoimmune attack into a controlled, specific intervention that can be reversed and does not require lifelong insulin dependence
2Ease of operation
If no disease-modifying therapy is available, then current treatments can manage symptoms, but patients have reduced life expectancy and chronic risk for complications
Solution Approach 1:
The patent employs preliminary action by using epitope-specific monoclonal antibodies or tolerance-inducing therapies to prevent or delay the onset of β cell destruction before complete autoimmune destruction occurs. By targeting pathogenic T cell epitopes early in the disease process, the therapy can preserve residual β cell function and delay the need for insulin dependence, improving long-term outcomes and life expectancy
Solution Approach 2:
The patent changes the fundamental parameter of immune recognition by targeting specific T cell epitopes rather than the entire insulin molecule or other pancreatic antigens. This parameter change from broad, non-specific immune suppression to epitope-specific modulation allows for more precise control of the autoimmune response, preserving protective immune functions while eliminating pathogenic responses against β cells
3Reliability
If T cell-mediated destruction of pancreatic β cells is targeted, then autoimmune destruction can be prevented, but new disease-modifying therapies must be developed and approved
Solution Approach 1:
The patent segments the complex autoimmune response in T1D by identifying and targeting specific T cell epitopes (such as Insulin B:9-23, GAD2:190-205, IA-2:610-626) rather than attempting to suppress the entire immune response. This segmentation allows for precise targeting of pathogenic T cells while preserving protective immune functions, creating a more manageable and specific therapeutic approach that can be developed through systematic identification of epitope-antibody pairs
Solution Approach 2:
The patent uses monoclonal antibodies as standardized, reproducible copies of specific immune responses that recognize and bind to pathogenic T cell epitopes. These monoclonal antibodies provide consistent, defined therapeutic agents that can be manufactured with precise control over their epitope-binding properties, simplifying development and regulatory approval compared to broader, less defined immunomodulatory therapies
Data Source
AI summary
Provided herein are T cell epitopes associated with Type 1 diabetes. Also provided are antigen-presenting cells presenting such epitopes. T cells reactive to such epitopes, and related compositions and therapies.