Tolerizing Agents for Antigen-Specific Immune Tolerance
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Solution Overview
Problem
Current enzyme and protein replacement therapies, as well as gene therapies, face challenges due to immunogenicity, leading to unwanted immune responses and limited therapeutic options for patients, particularly in autoimmune disorders where immune tolerance to self-antigens is compromised.
Innovation Solution
The technology involves administering compounds that modulate the T-cell immunoglobulin mucin (TIM) family receptors to induce antigen-specific or self-tolerance, reducing antigen-specific antibody titers and increasing regulatory T-cell populations, thereby mitigating immune responses and treating autoimmune disorders.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If enzyme or protein replacement therapy is administered to treat congenital disorders, then therapeutic effect is achieved, but unwanted immune response develops toward the enzyme or protein
Solution Approach 1:
The patent uses tolerizing agents as intermediary substances that mediate between the foreign enzyme/protein therapy and the patient's immune system. These agents induce immune tolerance by modulating the immune response, allowing the therapeutic enzyme or protein to function without triggering unwanted immune reactions that would otherwise neutralize the therapy or alter its pharmacokinetics
Solution Approach 2:
The patent applies preliminary immune tolerance induction before or during the administration of enzyme or protein replacement therapy. By pre-treating patients with tolerizing agents to establish immune tolerance, the therapy can be administered repeatedly without developing unwanted immune responses, addressing the problem before it manifests
2Reliability
If gene therapy is administered to treat congenital disorders, then promising therapeutic approach is achieved, but immunogenicity of carrier and genetic material becomes a major challenge
Solution Approach 1:
The patent employs tolerizing agents as intermediaries to reduce the immunogenicity of gene therapy carriers and genetic material. These agents modulate the immune system's response to the foreign DNA, RNA, or viral vectors used in gene therapy, preventing the development of anti-carrier antibodies that would otherwise counter-indicate treatment or prevent repeat dosing
Solution Approach 2:
The patent applies preliminary anti-action by using tolerizing agents to preemptively counteract the immunogenic response to gene therapy components. This preliminary immune modulation prevents the formation of neutralizing antibodies against the carrier or genetic material, thereby protecting the gene therapy from immune-mediated failure
3Reliability
If general immune suppression is used to treat autoimmune disorders, then immune tolerance to self-antigens is improved, but patients become immunocompromised and susceptible to opportunistic infections
Solution Approach 1:
The patent applies local quality by using antigen-specific tolerizing agents that selectively induce tolerance only to the specific self-antigens involved in the autoimmune disorder, rather than causing general immune suppression. This targeted approach restores immune tolerance locally to the affected antigens while preserving the patient's overall immune competence and resistance to opportunistic infections
Solution Approach 2:
The patent utilizes parameter changes by employing tolerizing agents that specifically alter the immune response parameters related to self-antigen recognition and tolerance, without changing the general immune suppression parameters. This selective parameter modification achieves immune tolerance to self-antigens while maintaining normal immune function against pathogens
Data Source
AI summary
Provided herein are compositions comprising amino acids, e.g., hydroxyamino acids, thioamino acids, or pharmaceutically acceptable salts thereof, that can be used to reduce immune intolerance in a subject. The compositions can be used, for example, to treat autoimmune disorders or in combination with an antigenic therapy, such as a protein or gene therapy, to improve the efficacy of the antigenic therapy.