PAGE5 Peptide MHC Complexes for Specific Cancer Immunotherapy
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Solution Overview
Problem
Current immunotherapeutic approaches for cancer treatment face challenges in accurately targeting tumor cells due to the scarcity of T cells recognizing tumor-associated antigen (TAA)-derived peptides with high affinity, and existing prediction methods generate false positives, making it difficult to identify suitable therapeutic targets with a sufficient therapeutic window.
Innovation Solution
Development of novel peptides derived from PAGE5, which form stable complexes with MHC molecules, and binding moieties that specifically target these complexes to induce a T cell response, utilizing RNA expression data to identify peptides with a therapeutic window for cancer therapy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If in silico algorithms are used to predict MHC-presented peptides, then peptide identification is accelerated, but false positive rate increases
Solution Approach 1:
The patent introduces experimental validation methods (mass spectrometry, HLA stability assays, peptide elution techniques) as intermediary steps between computational prediction and clinical application. These experimental intermediaries filter false positives from in silico predictions while maintaining the productivity benefits of computational screening.
Solution Approach 2:
The patent implements feedback loops where experimental data from mass spectrometry and HLA stability measurements are used to refine and validate computational predictions. This feedback mechanism allows continuous improvement of prediction accuracy while maintaining high-throughput screening capabilities.
2Reliability
If T cells with high affinity for TAA-derived peptides are selected during thymus maturation, then immune response specificity is improved, but T cell repertoire diversity decreases
Solution Approach 1:
The patent performs preliminary identification and characterization of high-affinity peptide-MHC complexes ex vivo before clinical application. By pre-selecting and validating specific peptide-MHC targets in the laboratory, the system compensates for the limited diversity of naturally selected T cells, enabling targeted immunotherapy against specific tumor antigens.
Solution Approach 2:
The patent alters the selection parameters by focusing on specific high-affinity peptide-MHC complexes rather than relying on natural T cell repertoire selection. By changing the selection criteria to target specific peptides with known high-affinity binding characteristics, the system achieves both specificity and controlled versatility.
3Productivity
If TAAs with high expression in tumor tissue are targeted, then therapeutic efficacy is improved, but off-tumor toxicity risk increases
Solution Approach 1:
The patent applies local quality by targeting specific peptide-MHC complexes that are locally unique to tumor cells. By identifying peptides that are presented by HLA molecules on tumor cells but not on normal cells (even when the parent protein is expressed in both), the system achieves high tumor specificity while minimizing off-target effects.
Solution Approach 2:
The patent segments the targeting approach by focusing on specific peptide epitopes rather than targeting entire proteins. This segmentation allows selective targeting of tumor-expressed peptide-MHC complexes while leaving the parent proteins in normal tissues unaffected, thereby reducing off-tumor toxicity.
Data Source
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AI summary
The present invention relates to novel peptides derived from P antigen family member 5 (PAGE5), 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.