Peptide-Based Tolerization for Multiple Sclerosis
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Solution Overview
Problem
Current therapies for multiple sclerosis (MS) are only partially effective, involve numerous and sometimes severe side effects, and do not specifically address the pathogenesis of MS by deleting or inhibiting pathogenic autoreactive cells without affecting normal immune cells.
Innovation Solution
Identification of peptides based on newly identified autoantigens TSTA-3 and RASGRP2 that can be used in a physiological solution for a tolerization approach, specifically coupling these peptides to red or white blood cells to induce antigen-specific tolerance in MS patients.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current antigen-nonspecific immunomodulating or immunosuppressive therapies are used for MS treatment, then immune response is modulated or suppressed, but beneficial regulatory cells and immune cells that serve protective functions are also inhibited and numerous severe side effects occur
Solution Approach 1:
The invention segments the immune response by targeting specific autoreactive T cell clones that recognize immunodominant peptides from autoantigens (MBP, PLP, MOG, TSTA3, RASGRP) while leaving other immune cells intact. This is achieved through antigen-specific tolerance induction using personalized peptide vaccines tailored to each patient's HLA genotype and T cell repertoire, thereby suppressing only the pathogenic subset of immune cells responsible for MS while preserving beneficial regulatory and protective immune functions.
Solution Approach 2:
The invention applies local quality by customizing the treatment to each patient's specific immunological profile. Personalized peptide vaccines are designed based on individual HLA class II alleles and patient-specific autoreactive T cell clones identified through T cell receptor sequencing. This ensures that immunosuppression is localized precisely to the patient's pathogenic T cell clones rather than globally suppressing the entire immune system, thereby reducing side effects while maintaining effectiveness.
2Object-affected harmful factors
If antigen-specific tolerance induction using personalized peptide vaccines is implemented, then pathogenic autoreactive T cells are specifically deleted or inhibited, but the complexity of identifying patient-specific T cell clones and customizing vaccines increases
Solution Approach 1:
The invention employs preliminary action by performing comprehensive T cell receptor sequencing and immunodominant peptide identification early in the disease course, preferably during clinically isolated syndrome or radiologically isolated syndrome stages before significant neurological disability develops. This early characterization of patient-specific autoreactive T cell clones and HLA alleles enables streamlined vaccine design and reduces the overall complexity and time required for personalized treatment development.
Solution Approach 2:
The invention uses computational algorithms and bioinformatics tools as intermediaries to bridge the gap between raw T cell sequencing data and personalized vaccine design. These computational intermediaries automatically analyze T cell receptor sequences, predict HLA-binding peptides, and generate optimized vaccine formulations, thereby reducing the manual complexity involved in personalized vaccine development while maintaining high specificity.
3Reliability
If immunodominant peptides are coupled to white or red blood cells for tolerization, then antigen-specific tolerance is induced, but the solubility and ease of administration in physiological solutions may be compromised
Solution Approach 1:
The invention utilizes physiological solutions (aqueous buffers) to dissolve and deliver personalized peptide vaccines, enabling easy administration through various routes such as intramuscular injection, subcutaneous injection, or oral delivery. The peptides are formulated in soluble forms that maintain stability and bioavailability in physiological conditions, thereby combining the effectiveness of antigen-specific tolerance induction with the convenience of easy administration without requiring complex coupling to blood cells.
Data Source
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AI summary
The disclosure relates to novel TSTA-3 and/or RASGRP2 peptides and a combination and a polypeptide or protein comprising such peptides. The peptides or polypeptides or proteins can particularly be used for the treatment and/or prevention of multiple sclerosis (MS), such as in a tolerization approach.