Lipidic Particles Induce Immune Tolerance
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Solution Overview
Problem
Protein therapeutics often face challenges due to their immunogenicity, leading to antibody formation that can abrogate protein activity and alter pharmacokinetic properties, necessitating methods to reduce immunogenicity and induce immune tolerance, especially for blood coagulation cascade proteins.
Innovation Solution
The use of lipidic compositions or particles comprising phosphatidylserine (PS), phosphatidylinositol (PI), and phosphatidylcholine (PC) or O-phospho-L-serine (OPLS) to incorporate antigens, which are administered subcutaneously, inducing immune tolerance by increasing TGF-β or IL-10 levels and reducing IL-6, IL-17, and co-stimulatory signals like CD40 and CD86.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If protein therapeutics are administered to treat blood coagulation disorders, then therapeutic efficacy is improved, but immunogenicity increases leading to antibody formation that abrogates protein activity
Solution Approach 1:
Lipidic particles comprising phosphatidylserine and phosphatidylcholine are used as intermediary carriers to deliver blood coagulation cascade proteins. These lipidic particles mask the immunogenic epitopes of the therapeutic proteins while facilitating their delivery to target sites, thereby reducing antibody formation while maintaining therapeutic efficacy
Solution Approach 2:
The patent modifies the physical and chemical parameters of protein delivery by incorporating proteins into lipidic particles with specific compositional ratios (phosphatidylserine:phosphatidylcholine). This parameter change alters the immunogenic properties of the proteins without changing their therapeutic function, reducing immunogenicity while preserving efficacy
2Duration of action of moving object
If protein therapeutics are administered repeatedly to maintain therapeutic levels, then therapeutic coverage is improved, but immune tolerance is reduced due to continuous immune system stimulation
Solution Approach 1:
The lipidic particle formulation is designed to induce immune tolerance in advance before repeated administrations begin. The specific lipid composition pre-conditiones the immune system to accept the therapeutic protein, allowing subsequent repeated administrations to maintain therapeutic levels without triggering immune responses or losing tolerance
3Ease of operation
If standard protein formulations are used for blood coagulation therapies, then ease of administration is maintained, but pharmacokinetic properties are altered by antibody formation
Solution Approach 1:
Lipidic particles serve as intermediary delivery vehicles that maintain ease of subcutaneous or intravenous administration while protecting the therapeutic protein from immune-mediated clearance. The particles modify pharmacokinetic properties by reducing antibody formation and altering distribution and clearance patterns
Data Source
Figure 1(A)a~1(A)b
Figure 1(A)c~1(A)d
Figure 1(B)
AI summary
This invention provides a method for inducing immune tolerance toward an antigen comprising the antigen in lipidic particles or lipidic compositions. The lipidic particles are made up of phosphatidylserine and phosphatidylcholine, or phosphatidylinositol and phosphatidylcholine. The lipidic compositions comprise the antigen and O-phospho-L- serine. Administration of these composition results in inducing immune tolerance to the antigen.