Antigen-Specific T Regulatory Cells for Autoimmune Suppression
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods for producing T regulatory cells are non-specific, leading to immunosuppressive effects that can be undesirable in responses to pathogenic infections and cancer, while there is a need for therapies to minimize autoimmune disorders and unfavorable responses to genetic disease treatments like hemophilia and Pompe's disease.
Innovation Solution
A method for producing antigen-specific T regulatory cells by transducing T cells with an expression vector encoding a T cell receptor that recognizes a specific antigen, followed by expansion ex vivo, using techniques such as retroviral transduction and stimulation with specific antigens and oligodeoxynucleotides.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If non-specific T regulatory cells are used to suppress immune responses, then autoimmune disorders are minimized, but immune responses to pathogenic infections and cancer are also suppressed
Solution Approach 1:
The patent segments the immune system's regulatory function by creating antigen-specific T regulatory cells that target only particular antigens (such as self-antigens in autoimmune diseases) while leaving other immune responses intact. This is achieved by transducing T cells with expression vectors encoding specific T cell receptors that recognize only the target antigen, thereby dividing the suppressive function into targeted compartments rather than applying blanket immunosuppression.
Solution Approach 2:
The patent applies local quality by endowing specific T regulatory cells with antigen-specific suppressive properties through genetic transduction. The transduced Tregs express T cell receptors that are locally tailored to recognize specific antigens (e.g., myelin basic protein in multiple sclerosis, insulin in type 1 diabetes), creating localized immunosuppression only where needed rather than systemic suppression.
2Manufacturing precision
If antigen-specific T regulatory cells are produced through transduction and expansion, then specificity is improved, but process complexity increases
Solution Approach 1:
The patent applies preliminary action by pre-transducing T cells with expression vectors encoding desired T cell receptors before expansion. The T cells are genetically modified in advance to express specific antigen-recognition capabilities, and then expanded ex vivo to generate large numbers of antigen-specific T regulatory cells. This preliminary genetic programming ensures that all expanded cells will be antigen-specific, eliminating the need for complex post-expansion sorting or selection processes.
Solution Approach 2:
The patent uses expression vectors as intermediaries to transfer specific T cell receptor genes into T regulatory cells. These vectors serve as mediators that carry the genetic information encoding antigen-specific TCRs from external sources into the target T cells, enabling the cells to acquire specific antigen recognition capabilities without direct genetic manipulation of each cell individually.
3Quantity of substance
If T cells are expanded ex vivo after transduction, then cell quantity increases, but production time extends
Solution Approach 1:
The patent maintains continuity of useful action by expanding transduced T regulatory cells ex vivo under optimized culture conditions that sustain continuous proliferation. The transduced Tregs are cultured with appropriate antigens and cytokines (such as IL-2) to maintain their suppressive function while enabling sustained expansion over multiple days, generating sufficient cell numbers for therapeutic application without interrupting the productive process.
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 method generates functionally active antigen-specific Tregs that inhibit effector T cells reactive to specific antigens, effectively reducing undesirable immune responses in autoimmune diseases and genetic disease treatments, as demonstrated by specific examples like hemophilia and multiple sclerosis.
Implementation Method 1
transducing T cells with an expression vector comprising a nucleotide sequence encoding a T cell receptor
Implementation Method 2
a T cell receptor that specifically recognizes the antigen
Implementation Method 3
expanding the transduced T cells ex vivo
Implementation Method 4
T regulatory cells suppress immune responses of other cells
Data Source
AI summary
The present invention generally relates to the production of antigen-specific T regulatory cells (Tregs). Such cells can be used in therapy to minimize undesirable immune responses such as those observed in autoimmunity and hemophilia and other diseases as well as in the response to protein therapy for genetic diseases. Methods for producing antigen specific Tregs and conditions for preferential expansion of functionally stable, specific Tregs are also provided.