Multimeric T-Cell Polypeptides for Specific Immune Modulation
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Solution Overview
Problem
Current immune response modulation technologies lack specificity and efficiency in activating or inhibiting T cells, as they rely on non-epitope-specific costimulatory proteins expressed on all T cells or large subsets, leading to uncontrolled immune responses.
Innovation Solution
Development of T-cell modulatory multimeric polypeptides (TMMPs) that incorporate epitope-presenting Wilms tumor peptides and immunomodulatory polypeptides, allowing for targeted modulation of T cell activity and immune response through specific binding to T cell receptors and costimulatory proteins.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If non-epitope-specific costimulatory proteins are used for T cell modulation, then ease of operation is improved, but specificity deteriorates
Solution Approach 1:
The patent divides the T cell modulation function into two separate components: epitope-specific TCR engagement and costimulatory protein engagement. By segmenting these functions and combining them in a controlled manner through the multimeric polypeptide structure, the system achieves both specificity (through epitope recognition) and ease of operation (through costimulatory engagement) without the drawbacks of non-specific costimulatory proteins.
Solution Approach 2:
The multimeric polypeptide acts as an intermediary that bridges the epitope-specific TCR and the costimulatory proteins. It presents the epitope to engage TCR while simultaneously providing costimulatory signals, thereby mediating between the need for specificity and the need for operational ease in a controlled, specific manner.
2Ease of operation
If costimulatory proteins expressed on all T cells are used, then ease of operation is improved, but reliability deteriorates
Solution Approach 1:
The patent applies local quality by making the costimulatory engagement specific to certain T cell subsets that express particular costimulatory proteins, rather than affecting all T cells uniformly. This localized approach maintains ease of operation for the target subset while improving reliability by avoiding unwanted effects on other T cell populations.
Solution Approach 2:
The system changes the parameter of costimulatory protein expression specificity by using multimeric polypeptides that engage specific costimulatory proteins on specific T cell subsets. This parameter change transforms the broad, uncontrolled activation into a targeted, reliable response while preserving operational ease for the intended target.
3Manufacturing precision
If epitope-specific TCR engagement is used, then specificity is improved, but device complexity increases
Solution Approach 1:
The patent merges the epitope-specific TCR engagement and costimulatory protein engagement into a single multimeric polypeptide structure. This combining approach maintains the high specificity of epitope targeting while reducing device complexity by integrating multiple functions into one component rather than requiring separate systems.
Solution Approach 2:
The multimeric polypeptide exhibits multi-functionality by simultaneously providing epitope presentation for TCR engagement and costimulatory signals. This universal design achieves specific T cell targeting without increasing complexity, as a single component performs multiple essential functions.
Data Source
AI summary
The present disclosure provides T-cell modulatory multimeric polypeptides that comprise an immunomodulatory polypeptide and that comprise an epitope-presenting Wilms tumor peptide. A T-cell modulatory multimeric polypeptide is useful for modulating the activity of a T cell, and for modulating an immune response in an individual.