Human ApoB100 T-Cell Epitopes for Targeted Inflammation Modulation
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Solution Overview
Problem
The regions of ApoB100 that activate T cells to induce inflammatory responses in atherosclerosis are not well understood, leading to uncontrolled foam cell formation and plaque development, which can result in adverse cardiovascular events.
Innovation Solution
Identification and utilization of novel ApoB100 T cell epitopes, such as SLFFSAQPFEITAST (p18) and IKHIYAISSAALSAS (p9), to modulate immune responses and potentially suppress or enhance T cell activity, thereby reducing atherosclerosis and other cardiovascular diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If T cell epitopes of ApoB100 are identified and targeted, then specific immune responses can be elicited to modulate inflammation, but the complexity of identifying and characterizing multiple epitopes increases
Solution Approach 1:
The patent segments the ApoB100 protein into multiple T cell epitopes (e.g., p18, p9, P101, P102, P103) with specific amino acid sequences. This segmentation allows the immune system to target specific regions of the protein, enabling precise modulation of inflammatory responses while managing the complexity through systematic classification of epitopes.
Solution Approach 2:
The patent utilizes HLA allele-specific epitopes, where the same ApoB100 sequence can be presented differently depending on the individual's HLA genotype. This parameter change approach allows for personalized immune responses tailored to specific HLA alleles, improving specificity while providing a framework for managing complexity through genetic stratification.
2Reliability
If foam cell formation is allowed to proceed uncontrolled, then atherosclerosis development occurs, but preventing this requires targeted immune modulation which increases treatment complexity
Solution Approach 1:
The patent extracts specific T cell epitopes from the ApoB100 protein sequence, isolating the critical regions that drive foam cell formation and atherosclerosis. By focusing therapy on these specific epitopes rather than the entire protein, the treatment becomes more targeted and manageable, improving reliability while reducing the complexity of immune modulation.
Solution Approach 2:
The patent employs HLA molecules as intermediaries that present ApoB100 epitopes to T cells. This intermediary mechanism allows for controlled immune activation, where the HLA-ApoB100-T cell interaction serves as a regulated pathway to modulate inflammation and prevent atherosclerosis, making the therapy more manageable and reliable.
3Adaptability or versatility
If multiple ApoB100 epitopes are characterized for different HLA alleles, then personalized treatment can be achieved, but the time required for epitope identification and characterization increases
Solution Approach 1:
The patent performs preliminary characterization of ApoB100 epitopes for multiple HLA alleles in advance, creating a reference database before treatment is needed. This preliminary action includes identifying epitopes for HLA-A, HLA-B, and HLA-C alleles, allowing for rapid matching and personalized treatment selection without time-consuming identification processes during actual therapy.
Solution Approach 2:
The patent develops a universal framework for characterizing epitopes across different HLA alleles (A, B, and C), creating a multi-functional system that can be applied to various patient populations. This universal approach enables personalized treatment while reducing time requirements through standardized characterization protocols and shared resources across different HLA types.
Data Source
AI summary
Provided herein are composition comprising novel epitopes of ApoB100, as well as sub-sequences, portions and modifications thereof, and uses thereof for treating adverse cardiovascular events, cardiovascular disease, atherosclerosis and certain liver disorders.