Shared Neoantigen Peptides for HLA-Matched Cancer Immunotherapy
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Solution Overview
Problem
Current cancer therapies, including vaccines, often come with serious side effects and high costs, and existing cancer vaccines using shared tumor antigens are limited by immune dampening effects and require individualized sequencing, making them inefficient for broad cancer treatment.
Innovation Solution
A pharmaceutical composition comprising one or more neoantigenic peptides that bind to HLA proteins, specifically targeting tumor-specific mutations present in a significant proportion of cancer patients, allowing for an immune response without the need for individual genome sequencing, and can be tailored to specific cancer types or populations based on common HLA subtypes and mutations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If patient-specific neoantigens are used to overcome immune dampening effects, then immune response efficacy is improved, but manufacturing complexity and cost increase due to required genome sequencing and personalized composition production
Solution Approach 1:
The patent segments the population into HLA subtype groups and identifies shared neoantigens within each segment. Instead of creating fully personalized vaccines for each patient, the invention divides the problem into manageable segments (HLA-A*02:01, HLA-A*24:02, etc.) and develops targeted compositions for each segment, reducing manufacturing complexity while maintaining immune response efficacy.
Solution Approach 2:
The patent creates representative neoantigen compositions that copy the essential immunogenic features of patient-specific neoantigens without requiring full personalization. By identifying recurrent mutations and shared neoantigens across multiple patients with the same HLA subtype, the invention produces standardized compositions that replicate the protective effect of personalized vaccines at reduced complexity.
2Manufacturing precision
If individual genome sequencing is performed to identify patient-specific neoantigens, then treatment precision is improved, but treatment time and cost increase
Solution Approach 1:
The patent performs preliminary identification of shared neoantigens and recurrent mutations across patient populations before clinical implementation. By pre-characterizing neoantigens associated with specific HLA subtypes and cancer types, the invention eliminates the need for time-consuming individual genome sequencing and analysis during patient treatment, while maintaining treatment precision through HLA-subtype-matched compositions.
Solution Approach 2:
The patent develops universal neoantigen compositions that can treat multiple patients sharing the same HLA subtype and cancer type. These compositions target recurrent mutations and shared neoantigens that appear across multiple individuals, allowing a single composition to serve multiple patients simultaneously, thereby reducing both time and cost while maintaining treatment precision for HLA-matched populations.
3Ease of manufacture
If shared tumor antigens are used in vaccines, then manufacturing simplicity is improved, but immune response is weakened due to immune dampening effects
Solution Approach 1:
The patent applies local quality by selecting specific neoantigens with high immunogenicity within each HLA subtype group. Instead of using all shared tumor antigens uniformly, the invention identifies and incorporates only those neoantigens derived from recurrent mutations that demonstrate strong T-cell recognition and immunogenicity in specific HLA-matched populations, thereby enhancing immune response while maintaining manufacturing simplicity.
Solution Approach 2:
The patent changes the parameter of antigen selection from generic shared tumor antigens to specific neoantigens derived from recurrent somatic mutations. By focusing on neoantigens with high mutation frequency and strong immunogenicity profiles within specific HLA subtypes, the invention transforms the quality of the antigen composition to overcome immune dampening effects while preserving ease of manufacture through standardized protocols.
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 composition effectively elicits an immune response against tumors in a large proportion of cancer patients, potentially improving treatment outcomes while reducing side effects and costs, as it can be formulated for specific cancer types and populations, enhancing the immune system's ability to target cancer cells without individualized sequencing.
Implementation Method 1
each at least one neoantigenic peptide comprising a tumor-specific neoepitope capable of binding to an HLA protein in a subject
Implementation Method 2
The composition effectively elicits an immune response against tumors in a large proportion of cancer patients
Data Source
AI summary
Disclosed herein in one aspect is a pharmaceutical composition comprising a plurality of neoantigenic peptides and a pharmaceutically acceptable carrier, each neoantigenic peptide comprising a tumor-specific neoepitope capable of binding to an HLA protein in a subject, each tumor-specific neoepitope comprising a tumor-specific mutation present in a tumor, wherein (a) the composition comprises neoantigenic peptides comprising tumor-specific mutations present in at least 1% of subjects in a population of subjects suffering from cancer; (b) the composition comprises neoantigenic peptides comprising tumor-specific neoepitopes which bind to HLA proteins present in at least 5% of subjects in the population; and (c) the composition comprises at least one neoantigenic peptide capable of eliciting an immune response against a tumor present in at least 5% of the subjects in the population of subjects suffering from cancer.