Multimeric T-Cell Polypeptides With Wilms Tumor Epitope Targeting
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Solution Overview
Problem
Current immune response modulation technologies are limited in specificity and efficiency, particularly in activating or inhibiting T cells, as they rely on non-epitope-specific costimulatory proteins that are expressed on all T cells or large subsets, lacking targeted activation or inhibition mechanisms.
Innovation Solution
Development of T-cell modulatory multimeric polypeptides (TMMPs) that combine an immunomodulatory polypeptide with an epitope-presenting Wilms tumor peptide, forming heterodimers or multimers with MHC polypeptides and optionally Ig Fc polypeptides, to specifically modulate T cell activity and immune responses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If non-epitope-specific costimulatory proteins are used to modulate T cells, then T cell activation or inhibition can be achieved, but specificity is reduced because the proteins are expressed on all T cells or large subsets
Solution Approach 1:
The patent combines an epitope-specific MHC peptide complex with a costimulatory protein into a single multimeric structure. This merging allows the molecule to simultaneously provide antigen-specific targeting through the MHC-peptide component and costimulatory signaling through the costimulatory protein component, thereby achieving both high specificity and reliable T cell modulation.
Solution Approach 2:
The invention creates a composite molecular structure consisting of multiple functional components: an MHC molecule, a peptide antigen, and a costimulatory protein. This composite structure integrates the targeting function of the MHC-peptide complex with the activation function of the costimulatory protein, enabling selective modulation of T cells that recognize the specific epitope while receiving costimulatory signals.
2Adaptability or versatility
If costimulatory proteins expressed on all T cells are used, then broad T cell coverage is achieved, but the ability to selectively activate or inhibit specific T cell populations is lost
Solution Approach 1:
By merging the epitope-specific MHC-peptide targeting module with the costimulatory protein module into a single multimeric entity, the invention achieves epitope-specific delivery of costimulatory signals. This ensures that only T cells expressing the cognate TCR for the specific epitope receive the costimulatory activation, thereby maintaining broad applicability across different epitope-specific T cell populations while preserving precise epitope-level targeting.
3Productivity
If conventional T cell modulation methods are used, then immune response modulation is achieved, but efficiency is limited due to lack of targeted activation mechanisms
Solution Approach 1:
The patent merges antigen recognition and costimulatory signaling into a single multimeric molecule, creating a highly efficient mechanism for T cell activation. This combined structure ensures that only T cells with the specific epitope-specific TCR receive both the antigen signal and the costimulatory signal simultaneously, dramatically improving the efficiency of targeted T cell activation compared to conventional methods that require separate delivery of these signals.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The TMMPs enhance targeted T cell activation or inhibition by binding with higher affinity to T cells expressing cognate co-immunomodulatory proteins, improving the specificity and efficacy of immune response modulation.
Implementation Method 1
the TCR is specific for a given epitope; however, the costimulatory protein not epitope specific and instead is generally expressed on all T cells or on large T cell subsets
Implementation Method 2
the targeted T cells are activated through engagement of costimulatory proteins found on the APC with counterpart costimulatory proteins the T cells
Data Source
AI summary
The present disclosure provides T-cell modulatory multi-merit 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.