Reengineered T-Cell Epitopes for Safer Allergy Immunotherapy
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Solution Overview
Problem
Current treatments for food allergies, particularly peanut allergy, are either ineffective or pose life-threatening risks, and traditional methods to identify T-cell epitopes are expensive and inefficient.
Innovation Solution
Development of peptide-based immunotherapy using rationally modified T-cell epitopes that are administered to induce tolerance without secondary effects, combined with the use of bacterial-derived epitopes to trigger targeted immune responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If traditional overlapping peptide methods are used to identify T-cell epitopes, then comprehensive coverage of allergen sequences is achieved, but the cost and time required increase significantly
Solution Approach 1:
The patent segments the allergen protein sequence into smaller, non-overlapping peptide fragments (e.g., 15-20 amino acids each) rather than using traditional overlapping peptides. This segmentation reduces redundancy and the total number of peptides that need to be synthesized and tested, thereby decreasing identification time and cost while maintaining comprehensive coverage of the allergen sequence
Solution Approach 2:
The patent develops a universal algorithmic approach that can predict T-cell epitopes across different allergens without requiring allergen-specific optimization. This multi-functional method can be applied to various food allergies (peanut, shellfish, milk, etc.) using the same core methodology, reducing overall research time and resource investment across multiple allergy types
2Adaptability or versatility
If crude peanut extract is used for immunotherapy, then broad allergen coverage is provided, but life-threatening anaphylactic reactions may occur
Solution Approach 1:
The patent extracts only the specific T-cell epitope sequences from within the complex peanut allergen structure, separating them from the rest of the allergen protein. This extraction creates a purified immunotherapy composition that contains only the essential immunogenic fragments needed to induce tolerance, eliminating the harmful components that could trigger anaphylaxis while maintaining therapeutic effectiveness
Solution Approach 2:
The patent applies local quality by focusing immunotherapy on specific T-cell epitope regions rather than using whole allergen extract. By targeting only the specific amino acid sequences that interact with T-cells (local regions of the protein), the therapy achieves precise immune modulation without exposing patients to the broader spectrum of allergenic components that could cause severe reactions
3Reliability
If rationally modified epitopes are used for immunotherapy, then binding affinity and efficacy are improved, but the complexity of epitope design increases
Solution Approach 1:
The patent systematically changes key parameters of the epitope sequences, including amino acid substitutions, deletions, and extensions, based on predicted binding affinity to MHC molecules and T-cell receptor interaction. These parameter modifications are guided by computational algorithms that evaluate multiple factors simultaneously, improving therapeutic efficacy while managing design complexity through structured optimization rather than trial-and-error approaches
Solution Approach 2:
The patent replaces manual, trial-and-error epitope design with computational algorithms and in-silico prediction tools. This substitution of mechanical/manual processes with automated computational systems enables systematic evaluation of numerous epitope variants, prediction of binding affinities, and optimization of sequences for maximum immunogenicity, thereby improving efficacy while reducing the practical complexity of the design process
Data Source
AI summary
The present disclosure relates to pharmaceutical compounds and compositions and methods for treating an allergy and Crohn's disease. Methods for treating an allergy can include (a) predicting potential epitopes based proteomes of microbiome and that of an allergen, (b) filtering the potential epitopes obtained in step a) to result in a list of epitopes; and (c) reengineering the list of epitopes obtained in step b) to result in the new epitope. Methods for treating Crohn's disease can include (a), identifying one or more binding regions of an HLA class II protein and/or hemagglutinin to I2 superantigen; (b) determining a first peptide sequence corresponding to the one or more binding regions, and (c) producing a peptide inhibitor having a second peptide sequence that is a mutation of the first peptide sequence, wherein the second peptide sequence has a stronger binding affinity to the I2 superantigen than the first peptide sequence.