Mutated GNAS Peptide Mixtures for PMP Immunotherapy
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Solution Overview
Problem
Current treatments for pseudomyxoma peritonei (PMP), a rare abdominal cancer, are limited, especially for patients who cannot be cured by surgery, with poor responses to systemic chemotherapy and a lack of effective targeted therapies, and there is a need for innovative approaches to manage this debilitating and ultimately fatal condition.
Innovation Solution
Development of peptide mixtures and T-cell preparations specific to mutated GNAS peptides, which are used to elicit an immune response, combined with pharmaceutical formulations and checkpoint inhibitors to provide prophylaxis and treatment options for PMP and other GNAS-mutated cancers.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional treatments (systemic chemotherapy, angiogenesis inhibitors) are used for non-resectable and recurrent PMP, then treatment options are available, but treatment effectiveness is poor and quality of life deteriorates
Solution Approach 1:
The invention segments the tumor antigen into specific mutated peptide sequences (such as R201C and R201H variants of GNAS protein) that can be individually targeted. This segmentation allows the immune system to focus on specific mutated regions rather than the entire tumor mass, enabling more precise and effective immune recognition and attack against PMP cells expressing these specific mutations.
Solution Approach 2:
The patent uses peptide mixtures and T-cell preparations as intermediary agents between the patient's immune system and the tumor cells. These intermediaries (customized peptide vaccines and expanded T-cells) mediate the immune response by presenting mutated GNAS peptides to T-cells, which then recognize and attack tumor cells expressing the same mutations, bridging the gap between immune recognition and tumor destruction.
2Adaptability or versatility
If targeted therapies are developed for GNAS-mutated cancers, then treatment specificity is improved, but treatment options remain limited for patients who cannot be cured by surgery
Solution Approach 1:
The invention changes the parameter of treatment approach from conventional chemotherapy to personalized immunotherapy based on the specific mutated peptides identified in each patient's tumor. By analyzing the unique GNAS mutations present and customizing the peptide mixture accordingly, the treatment adapts to the specific molecular characteristics of each patient's cancer, improving both versatility and response rate.
Solution Approach 2:
The patent employs preliminary molecular characterization of the tumor to identify specific GNAS mutations before treatment initiation. This preliminary action involves sequencing and analyzing the tumor DNA/RNA to determine which mutated peptides are present, allowing the customized peptide vaccine and T-cell preparation to be tailored in advance to the patient's specific mutation profile, ensuring optimal treatment effectiveness from the start.
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 peptide mixtures and T-cell preparations specifically targeting GNAS mutations induce a strong immune response, potentially leading to effective prophylaxis and treatment of PMP and other GNAS-mutated cancers, improving patient outcomes by enhancing anti-tumor immunity and overcoming treatment limitations.
Implementation Method 1
T-cell mixtures and T-cell preparations comprising T-cells specific for such peptides when presented on MHC molecules
Data Source
AI summary
A peptide mixture suitable for eliciting an immune response, comprising a first peptide and a second peptide. The first peptide comprises a first sequence of at least (8) amino acids, wherein said first sequence has at least 75% sequence identity to a first region of (8) amino acids of SEQ ID NO: 11. This first region includes position (201) of the SEQ ID NO: 11 such that the first sequence includes the amino acid in position (201) of the SEQ ID NO: 11. The second peptide comprises a second sequence of at least (8) amino acids, wherein said second sequence has at least 75% sequence identity to a second region of (8) amino acids of SEQ ID NO: 12. This second region includes position (201) of the SEQ ID NO: 12 such that the second sequence includes the amino acid in position (201) of the SEQ ID NO: 12.