Engineered Flt3L Variants for Therapeutic Immune Tolerance
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Solution Overview
Problem
Existing therapies fail to effectively prevent unwanted immune responses against therapeutic agents, leading to detrimental effects such as allergic reactions and autoimmune diseases.
Innovation Solution
Administration of engineered Fms Related Receptor Tyrosine Kinase 3 Ligand (Flt3L) proteins, either alone or fused with albumin or the Fc domain of IgG1, to induce immunotolerance by preventing immune responses to therapeutic molecules.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional therapies are administered to treat diseases, then therapeutic effects are achieved, but unwanted immune responses such as allergic reactions and autoimmune diseases occur
Solution Approach 1:
The patent applies preliminary anti-action by administering FLT3L variants before exposure to therapeutic agents to pre-condition the immune system. This pre-treatment induces regulatory T cells and tolerogenic dendritic cells that prevent subsequent unwanted immune responses against therapeutic proteins, while maintaining the ability to mount effective immune responses against pathogens.
Solution Approach 2:
The FLT3L variant acts as an intermediary molecule that mediates between the therapeutic agent and the immune system. By binding to FLT3 receptors on dendritic cells and other immune cells, it modulates their function to promote tolerance rather than activation, thereby preventing harmful immune responses without directly interacting with the therapeutic protein itself.
2Object-affected harmful factors
If immune responses are blocked to prevent allergic reactions, then safety is improved, but productive immune responses against pathogens may be compromised
Solution Approach 1:
The patent applies local quality by creating spatial and functional differentiation in immune responses. FLT3L treatment induces tolerance specifically against therapeutic proteins through mechanisms involving regulatory T cells and tolerogenic dendritic cells, while leaving the immune system's ability to respond to pathogens intact. This localized tolerance prevents allergic reactions without compromising general immune defense.
Solution Approach 2:
The patent changes the functional parameters of immune cells through FLT3L treatment. This includes altering the differentiation pathways of dendritic cells toward tolerogenic phenotypes, modulating T cell activation thresholds, and changing cytokine production profiles. These parameter changes enable selective tolerance to therapeutic proteins while maintaining pathogen recognition and response capabilities.
Data Source
AI summary
The current disclosure describes compositions and methods that may be administered to prevent immune responses against therapeutic molecules. The disclosure provides for a composition comprising a polypeptide comprising an engineered Fms Related Receptor Tyrosine Kinase 3 Ligand (Flt3L) protein. Also described is a method of treatment comprising: administering to a subject in need thereof, an effective amount of an engineered Flt3L protein of the disclosure. Methods also relate to a method for inducing immunotolerance in a subject in need thereof comprising, the method comprising administering to the subject an engineered Flt3L protein of the disclosure.