Liver-Targeted Antigen Conjugates for Immune Tolerance Induction
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing approaches to induce tolerance to antigens that elicit unwanted immune responses, such as in transplant rejection, autoimmune diseases, and allergies, are limited in their effectiveness and specificity, particularly in targeting antigens to liver cells for immune tolerance induction.
Innovation Solution
Compositions comprising a compound with a specific structure (Formula 1) that includes an antigenic region (X), a linker moiety (Y), and a liver-targeting moiety (Z) are used to deliver antigens to liver cells, facilitating their processing and inducing immune tolerance.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If antigens are targeted to liver cells using existing approaches, then immune tolerance induction is achieved, but the effectiveness and specificity are limited
Solution Approach 1:
The patent employs composite structures consisting of antigens conjugated to liver-targeting moieties (such as galactose or asialoglycoprotein receptor ligands). This composite approach enables specific targeting to liver cells while maintaining antigen immunogenicity, thereby improving the reliability of immune tolerance induction without requiring complex delivery systems
Solution Approach 2:
The patent uses liver-specific receptors (such as asialoglycoprotein receptors) as intermediaries to mediate the delivery of antigens to liver cells. These natural receptors serve as bridges between the administered antigen conjugates and their intracellular targets, achieving specific targeting through biologically inherent pathways rather than engineered complex delivery mechanisms
2Productivity
If antigens are delivered to specific cell types in the liver, then antigen processing is enhanced, but the complexity of the delivery system increases
Solution Approach 1:
The patent leverages the liver's natural antigen-presenting cells and processing mechanisms to handle the delivered antigens. Once the antigen-conjugate reaches the liver cell via receptor-mediated endocytosis, the cell's own processing machinery (proteasomes, MHC molecules) performs the antigen processing, eliminating the need for complex external processing systems
Solution Approach 2:
The patent modifies the physical-chemical parameters of antigens by conjugating them to liver-targeting moieties. This parameter change (adding a targeting group) redirects the antigen to liver cells where processing is enhanced, achieving improved productivity through simple chemical modification rather than complex delivery infrastructure
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 compositions effectively deliver antigens to liver cells, enhancing antigen processing and inducing tolerance, thereby reducing unwanted immune responses to therapeutic agents, food antigens, and autoimmune diseases, including autoimmune disorders and allergies.
Implementation Method 1
Z comprises a liver-targeting moiety... effectively deliver antigens to liver cells
Data Source
AI summary
Several embodiments of the present disclosure relate to therapeutic compositions configured to target the liver of a subject and that are useful in the treatment or prevention of one or more of transplant rejection, autoimmune disease, food allergy, and immune response against a therapeutic agent. In several embodiments, the compositions are configured to target the liver and deliver antigens to which tolerance is desired. In several embodiments, the compositions are configured for clearance of a circulating protein or peptide or antibody associated with one or more of the above-mentioned maladies. Methods and uses of the compositions for induction of immune tolerance are also disclosed herein.