Cyclic Peptide Immunotherapy via Selective Cleavage
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Solution Overview
Problem
Current immunotherapeutic agents face challenges in specificity, tumour penetration, and manufacturing complexity for effectively targeting malignant cells, with existing methods often relying on targeting moieties and classical antigen processing pathways.
Innovation Solution
A cyclic peptide comprising a T cell antigen peptide that is not capable of eliciting a T cell response in its cyclised form, but becomes active upon selective cleavage in the vicinity of unwanted cells, allowing direct binding to MHC molecules or CD1 molecules without internalization, thereby enhancing specificity and tumour penetration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional immunotherapeutic agents use targeting moieties and classical antigen processing pathways, then they can target malignant cells, but they suffer from reduced specificity and poor tumour penetration
Solution Approach 1:
The invention extracts the T cell antigen peptide from the complex classical antigen processing pathway and delivers it directly to the cell surface via a conjugate system, bypassing the need for internalization and MHC class I processing, thereby improving tumour penetration and specificity
Solution Approach 2:
The patent uses a conjugate as an intermediary that links the T cell antigen peptide to a cell binding partner, enabling direct delivery to tumour cells without requiring the peptide to undergo classical antigen processing, thus enhancing targeting effectiveness
2Power
If ricin is used to deliver cytotoxic T cell epitopes into the MHC Class I pathway, then tumour cells can be lysed, but the agent lacks selectivity and binds to most cell types
Solution Approach 1:
The conjugate is designed with a cell binding partner that provides local specificity for tumour cells, ensuring that the cytotoxic T cell epitope is delivered only to the intended target, thereby maintaining power while improving selectivity
Solution Approach 2:
The invention changes the delivery mechanism from a non-specific toxin like ricin to a targeted conjugate system that can be optimized for tumour-specific binding, altering the key parameter of cellular selectivity while preserving cytotoxic capability
3Reliability
If T cell antigen peptides are internalized and processed through classical pathways, then they can be presented by MHC molecules, but the process is inefficient and reduces tumour penetration
Solution Approach 1:
The T cell antigen peptide is pre-loaded onto the conjugate outside the cell, eliminating the need for internalization and subsequent processing steps, thereby simplifying the overall process and improving tumour penetration while ensuring reliable antigen presentation
Solution Approach 2:
Instead of allowing the antigen to enter the cell and be processed through the classical pathway, the invention inverts the process by delivering the processed antigen directly to the cell surface, bypassing the complex intracellular processing steps
4Reliability
If complex conjugates with multiple components are used for re-directed immunotherapy, then targeting specificity can be improved, but manufacturing complexity increases
Solution Approach 1:
The conjugate merges the T cell antigen peptide and cell binding partner into a single bifunctional molecule, maintaining targeting specificity while simplifying manufacturing compared to separate multi-component systems that would require complex assembly
Data Source
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AI summary
The invention provides an agent comprising: a cyclic peptide comprising a T cell antigen peptide; wherein in cyclised form the T cell antigen peptide is not capable of eliciting a T cell response; and wherein the T cell antigen peptide is rendered capable of eliciting a T cell response by selective cleavage of one or more cleavage sites in the cyclic peptide. The agent may be used to prevent or treat a condition characterised by the presence of unwanted cells.