Lengsin-Derived Peptides for Targeted Cancer Immunotherapy
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Solution Overview
Problem
Current immunotherapeutic approaches for cancer treatment face challenges in accurately predicting peptide-MHC presentation by tumor cells, leading to inefficiencies and potential toxicity due to off-target effects, as existing methods rely on protein expression data and do not account for intracellular processing, and there is a scarcity of T cells recognizing tumor-associated antigens with high affinity.
Innovation Solution
Development of novel peptides derived from Lengsin (LGSN) that form stable complexes with MHC molecules, along with binding moieties that specifically target these peptides, utilizing RNA expression data to identify therapeutic windows and minimize toxicity, and employing recombinant MHC molecules and T cell receptors engineered for enhanced affinity and specificity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If protein expression data is used to identify therapeutic targets, then the process is simple and fast, but the accuracy is low and leads to false positives due to not accounting for intracellular processing
Solution Approach 1:
The patent replaces the conventional protein expression measurement approach with a computational prediction system that integrates multiple data types (RNA expression, protease cleavage sites, MHC binding affinity) through in silico algorithms. This substitution of mechanical/biochemical methods with computational modeling achieves higher accuracy in predicting actual peptide-MHC presentation while maintaining operational efficiency.
2Reliability
If T cells with high affinity for tumor-associated antigens are sought, then the therapeutic effectiveness is improved, but the scarcity of such T cells in the circulating repertoire makes detection difficult
Solution Approach 1:
The patent performs preliminary identification and characterization of tumor-associated peptide antigens and their presentation by MHC molecules on tumor cells before attempting to detect or engineer T cells. By pre-validating the target peptides through RNA expression analysis and MHC binding prediction, the system creates a reliable target for subsequent T cell identification or engineering efforts, making the detection of rare high-affinity T cells more feasible.
3Ease of manufacture
If conventional immunotherapeutic reagents are used, then development is straightforward, but off-target toxicity occurs due to lack of specificity
Solution Approach 1:
The patent applies local quality by ensuring that immunotherapeutic reagents target specifically validated tumor-associated peptides that are uniquely presented on tumor cells rather than broadly expressed antigens. By selecting peptides based on their specific presentation on tumor MHC molecules and their unique amino acid sequences, the therapy achieves localized specificity at the molecular level, directing immune attack precisely to tumor cells while sparing healthy tissues.
Data Source
AI summary
The present invention relates to novel peptides derived from Lengsin (LGSN), complexes comprising such peptides bound to recombinant MHC molecules, and cells presenting said peptide in complex with MHC molecules. Also provided by the present invention are binding moieties that bind to the peptides and/or complexes of the invention. Such moieties are useful for the development of immunotherapeutic reagents for the treatment of diseases such as cancer.