APC-Targeted Tolerance Constructs for Selective Immune Suppression
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Solution Overview
Problem
Existing immunosuppressive drugs for autoimmune diseases, allergic reactions, and graft rejection cause non-selective immune suppression, leading to severe side effects such as immunodeficiency and decreased cancer immunosurveillance.
Innovation Solution
Development of tolerance-inducing constructs that deliver disease-specific antigens to antigen-presenting cells via targeting units, inducing regulatory T cells and suppressing effector T cell responses without triggering inflammatory immune reactions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If broad-acting immunosuppressive drugs are used to prevent or reduce undesirable immune responses, then immune suppression is achieved, but severe side effects occur including immunodeficiency and increased susceptibility to infections
Solution Approach 1:
The patent segments the immune system response by creating antigen-specific tolerogenic constructs that target only the pathological immune response against specific antigens (self-antigens, allergens, alloantigens, or xenoantigens) while leaving the rest of the immune system intact. This is achieved through constructs comprising an antigenic unit combined with tolerogenic moieties that selectively induce tolerance to the specific antigen without broad immunosuppression, thereby maintaining immune surveillance against infections and cancer.
Solution Approach 2:
The patent applies local quality by creating localized tolerogenic effects at the site of antigen presentation. The constructs are designed to be presented by specific antigen-presenting cells (APCs) in a tolerogenic manner, inducing antigen-specific regulatory T cells locally without affecting the overall immune system. This allows immunosuppression to be confined to the specific antigen-targeted pathway while preserving immune function elsewhere.
2Duration of action of stationary object
If conventional immunosuppressive drug therapy is used to maintain immunosuppression, then unwanted immune responses are suppressed, but the therapy must be life-long and causes non-selective immune suppression
Solution Approach 1:
The patent segments the immunosuppressive approach into antigen-specific components. Instead of life-long broad immunosuppression, the constructs are designed to induce long-lasting antigen-specific tolerance through the generation of regulatory T cells. The tolerogenic constructs comprise specific antigenic units combined with tolerogenic moieties that create durable, targeted immune tolerance, potentially reducing or eliminating the need for continued therapy while maintaining selectivity.
Solution Approach 2:
The patent applies preliminary action by using tolerogenic dendritic cells or other tolerogenic APCs that are pre-conditioned or engineered to present antigens in a tolerogenic manner. This preliminary tolerogenic presentation induces long-lasting regulatory T cell responses that provide prolonged protection against unwanted immune responses without requiring continuous administration of immunosuppressive agents, thereby achieving both duration and selectivity.
3Reliability
If broad-acting immunosuppressive drugs are used to treat autoimmune diseases or graft rejection, then immune responses are suppressed, but cancer immunosurveillance is decreased
Solution Approach 1:
The patent segments the immune response into pathological and protective components. The antigen-specific tolerogenic constructs selectively suppress only the pathological immune responses against specific antigens (self-antigens in autoimmune diseases, alloantigens in graft rejection, or xenoantigens in xenotransplantation) while preserving the immune system's ability to perform cancer immunosurveillance and fight infections. This selective segmentation allows treatment of immune diseases without compromising protective immune functions.
Solution Approach 2:
The patent applies local quality by creating localized tolerogenic effects that are confined to specific antigen-specific immune pathways. The constructs induce tolerance locally at the level of antigen-presenting cells and antigen-specific T cells, leaving the broader immune surveillance mechanisms intact and functional. This localized approach suppresses harmful immune responses while preserving cancer immunosurveillance capabilities.
Data Source
AI summary
The present disclosure relates to tolerance-inducing constructs for inducing tolerance, such as by targeting the tolerance-inducing construct to antigen presenting cells (APCs). Further disclosed are polynucleotides, vectors, host cells, pharmaceutical compositions and kits comprising said tolerance-inducing construct. Also disclosed are tolerance-inducing constructs and compositions for use in the treatment of immune disorders, such as in the prophylactic or therapeutic treatment of autoimmune diseases, allergic disease and graft rejection.