Tolerance-Inducing Constructs for Antigen-Specific Immune Modulation
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Solution Overview
Problem
Current immunosuppressive therapies for autoimmune diseases, allergic reactions, and graft rejection often require lifelong administration and are associated with severe side effects due to their non-selective action, leading to increased susceptibility to infections and decreased cancer immunosurveillance.
Innovation Solution
The development of tolerance-inducing constructs that comprise an antigen unit and a targeting unit capable of interacting with antigen-presenting cells (APCs) in a non-inflammatory manner, allowing for the presentation of antigens in a tolerance-inducing context, thereby inducing antigen-specific tolerance.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If broad-acting immunosuppressive drugs are used to prevent undesirable immune responses, then immunosuppression is achieved, but severe side effects occur including increased susceptibility to infections and decreased cancer immunosurveillance
Solution Approach 1:
The invention segments the immune system's function by creating antigen-specific tolerance rather than broad immunosuppression. The tolerogenic dendritic cells are engineered to present specific self-antigens or alloantigens to induce antigen-specific regulatory T cells, thereby suppressing only the unwanted immune response against particular antigens while leaving the rest of the immune system intact and functional for fighting infections and cancer.
Solution Approach 2:
The invention applies local quality by making the immunosuppressive effect targeted and localized to specific antigens. The dendritic cells are modified to express particular self-antigens or alloantigens on their surface, creating a localized tolerogenic effect only where and when these specific antigens are presented, rather than causing systemic immunosuppression affecting the entire immune system.
2Reliability
If conventional immunosuppressive therapy is administered to maintain immunosuppression, then prevention of undesirable immune responses is achieved, but lifelong treatment is required
Solution Approach 1:
The invention employs preliminary action by administering tolerogenic dendritic cells loaded with self-antigens or alloantigens to establish long-lasting antigen-specific tolerance. This preliminary tolerization induces the formation of regulatory T cells that provide lasting suppression of unwanted immune responses, potentially eliminating the need for lifelong continuous immunosuppressive therapy.
Solution Approach 2:
The invention enables self-service by creating an endogenous tolerance mechanism where the patient's own immune system generates regulatory T cells that continuously suppress unwanted immune responses against specific antigens. This self-sustaining tolerogenic mechanism reduces or eliminates the need for ongoing external immunosuppressive drug administration.
3Reliability
If broad-acting immunosuppressive drugs are used, then unwanted immune responses are suppressed, but non-selective action causes severe side effects
Solution Approach 1:
The invention segments the immunosuppressive effect to be antigen-specific rather than broad. The dendritic cells are engineered to present only specific self-antigens or alloantigens, creating a segmented and targeted tolerogenic effect that suppresses only the unwanted immune response against those particular antigens while leaving other immune functions unaffected.
Solution Approach 2:
The invention applies local quality by making the immunosuppressive effect targeted and localized to specific antigens. The dendritic cells are modified to express particular self-antigens or alloantigens on their surface, creating a localized tolerogenic effect only where and when these specific antigens are presented, rather than causing systemic immunosuppression affecting the entire immune system.
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
These constructs effectively induce antigen-specific tolerance, reducing the risk of immune response-related complications, while minimizing the impact on the general immune system, thus avoiding increased susceptibility to infections and maintaining cancer immunosurveillance.
Implementation Method 1
a targeting unit that interacts with surface molecules on APCs, such as dendritic cells, in a non-inflammatory or tolerogenic manner which leads to the presentation of the antigen in the absence of activation
Data Source
AI summary
The present disclosure relates to constructs and compositions for use in the treatment of conditions involving undesired immune reactions, such as in the prophylactic or therapeutic treatment of autoimmune diseases, allergic disease and graft rejection.