Universal MSI Cancer Vaccine via Shared Frame-Shift Peptides
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Solution Overview
Problem
Current cancer vaccines face challenges in developing a universal solution due to the variability of tumor neoantigens among cancer cells, particularly in microsatellite instability (MSI) tumors, which do not follow the general rule of tumor-associated and tumor-specific antigens, making it difficult to design an effective universal cancer vaccine.
Innovation Solution
A method for selecting a collection of frame-shift peptides (FSPs) to produce a universal cancer vaccine peptide collection (CVP) by identifying shared FSPs across MSI tumors, modifying their amino acid sequences if necessary, and encoding them in nucleic acid collections for use in vaccine vectors to target MSI cancers, including both hereditary and sporadic cases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If a universal cancer vaccine is designed to target shared tumor neoantigens across multiple cancer types, then the vaccine can be applied broadly to many patients, but the effectiveness is reduced because tumor neoantigens vary significantly among cancer cells and patients
Solution Approach 1:
The patent applies universality by designing a vaccine that targets frame-shift peptides shared across multiple MSI cancer types rather than patient-specific neoantigens. The vaccine composition includes peptides derived from multiple genes (e.g., MSH2, MLH1, MSH6, PMS2) that are commonly mutated in MSI tumors, enabling a single vaccine formulation to be effective across diverse cancer types and patients with MSI instability.
Solution Approach 2:
The patent applies local quality by focusing on specific regions of proteins where frame-shift mutations occur due to microsatellite instability. Instead of targeting the entire protein, the vaccine uses truncated peptides from the C-terminus of mutated genes, capturing the unique neoantigen regions created by frame-shift mutations while excluding normal protein sequences that could trigger autoimmunity.
2Reliability
If tumor-specific neoantigens are targeted to avoid self-tolerance and autoimmunity, then immune response is enhanced, but the variability among patients prevents development of a universal vaccine
Solution Approach 1:
The patent identifies and targets frame-shift peptides that are universally present in MSI tumors regardless of patient origin. By focusing on peptides derived from homologous regions of MMR genes across different cancer types (colorectal, endometrial, gastric, etc.), the vaccine achieves both tumor-specificity and universal applicability.
Solution Approach 2:
The patent extracts only the frame-shift peptide portions from mutated genes, separating these neoantigens from the normal protein sequences. This extraction ensures that only the mutated, tumor-specific regions are presented to the immune system, eliminating self-tolerance issues while maintaining universality across MSI patients.
3Adaptability or versatility
If a vaccine targets shared FSPs across MSI tumors, then a universal off-the-shelf vaccine can be developed, but the risk of autoimmune responses increases due to potential similarity with normal proteins
Solution Approach 1:
The patent applies local quality by using truncated peptide sequences from the C-terminus of frame-shift mutated genes. These truncated peptides represent only the novel sequence created by the frame-shift mutation, which is absent from normal proteins. This localized targeting ensures tumor-specificity while minimizing autoimmune risk.
Solution Approach 2:
The patent extracts and isolates only the frame-shift peptide sequences, separating them from any sequences that might be similar to normal proteins. By using only the mutated C-terminal portions, the vaccine presents purely neoantigenic sequences that should not trigger autoimmune responses against normal tissues.
Data Source
AI summary
This invention relates to a method of selecting a collection of frame-shift peptides (CFSPs) to produce a universal cancer vaccine peptide collection (CVP) for prophylaxis and treatment of patients with hereditary and sporadic micro-satellite instability (MSI) tumors. This invention relates as well to a method of producing a CVP by selecting a subset of frame-shift peptides (FSPs) from the CFSP and optionally modifying the FSP's amino acid (aa) sequence to generate modified FSPs (mFSPs). The invention further relates to nucleic acid collections encoding a CVP of FSPs and/or mFSPs in one or more vaccine vectors that can be used also simultaneously. These CVPs, nucleic acids and vectors are used for the prophylaxis or treatment of MSI cancers.