Tolerogenic Composition for Multiple Sclerosis Autoantigen Targeting
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Solution Overview
Problem
Current treatments for multiple sclerosis (MS) face challenges in identifying and targeting specific autoantigens, which hampers the effectiveness of antigen-specific immunotherapies, as the optimal autoantigens involved in MS pathogenesis remain unknown.
Innovation Solution
Identification of novel autoantigens such as FABP7, PROK2, RTN3, and SNAP91, which are used to develop a tolerogenic composition that induces antigen-specific T-cell tolerance by administering therapeutic T-cell epitopes or nucleic acids encoding these epitopes, or by exposing antigen-presenting cells to them, to treat MS patients.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional immunotherapies are used for multiple sclerosis, then general immune suppression is achieved, but specific targeting of autoantigens is lost leading to reduced treatment precision
Solution Approach 1:
The patent segments the complex task of identifying MS autoantigens by using a library of PrESTs (recombinant protein epitope signature tags) that represent specific peptide sequences from potential autoantigens. This segmentation allows systematic screening of T-cell responses against individual epitopes rather than whole proteins, making the complex identification process manageable and precise
Solution Approach 2:
The patent introduces PrESTs as intermediary molecules that bridge the gap between known protein sequences and unknown autoantigen targets. These PrESTs serve as mediators that can be systematically tested against patient T-cells to identify which specific epitopes trigger autoimmune responses, thereby simplifying the identification process while maintaining diagnostic accuracy
2Reliability
If antigen-specific immunotherapy is developed, then treatment precision is improved, but the unknown optimal autoantigens hamper effectiveness
Solution Approach 1:
The patent performs preliminary identification of autoantigens by screening patient T-cells against a comprehensive library of PrESTs before developing the actual immunotherapy. This preliminary action identifies which specific epitopes are targeted by autoreactive T-cells, providing the necessary information to design effective antigen-specific therapies without guessing which autoantigens are involved
Solution Approach 2:
The patent employs a feedback mechanism where T-cell responses to PrESTs are measured and used to identify specific autoantigen targets. This feedback information about which epitopes elicit strongest responses guides the selection of antigens for immunotherapy development, ensuring treatment is based on actual patient-specific immune responses rather than assumptions
3Measurement precision
If T-cell activation is measured against multiple antigens, then diagnostic accuracy is improved, but the complexity of the screening process increases
Solution Approach 1:
The patent merges multiple diagnostic functions into a single screening platform that tests T-cell responses against a library of PrESTs representing multiple potential autoantigens simultaneously. This combining approach maintains high diagnostic accuracy by evaluating multiple antigens while simplifying the overall process compared to performing separate tests for each suspected autoantigen
Data Source
AI summary
Described herein are tolerogenic compositions for use in a method of treatment for multiple sclerosis (MS) in a MS subject exhibiting T-cell autoreactivity against an endogenous epitope corresponding to a T-cell epitope comprising a sequence of at least 8 consecutive amino acid residues differing from a sub-sequence of SEQ ID NO: 5 by 0-2 residue substitutions, deletions and/or insertions, or the composition comprising a nucleic acid encoding said therapeutic T-cell epitope. Also described are methods for determining antigen-specific T-cell activation in a test subject, comprising providing a test sample derived from the test subject comprising viable T-cells; determining antigen-specific activation of the T-cells of the test sample in vitro in response to a test antigen comprising a T-cell epitope; and comparing the determined antigen-specific activation to a relevant reference to determine the degree of MS-related autoimmunity in the test subject.