Multi-HLA Binding Polypeptide Vaccine Epitopes
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Solution Overview
Problem
Current cancer vaccines are poorly immunogenic and fail to benefit most patients due to inter-individual tumor genomic heterogeneity, making it challenging to scale HLA-specific cancer vaccines to large populations effectively.
Innovation Solution
Identification of T cell epitopes from cancer-associated antigens that can bind to multiple class I HLA molecules in a high proportion of individuals, allowing for the development of polypeptides and pharmaceutical compositions that induce specific immune responses against tumor cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If HLA-specific cancer vaccines are developed for each patient based on inter-individual tumor genomic heterogeneity, then the vaccine effectiveness is improved, but the manufacturing complexity and scalability deteriorate
Solution Approach 1:
The patent identifies T cell epitopes that can bind to multiple class I HLA molecules across different individuals, creating a universal vaccine composition that functions effectively for a broad population rather than requiring individual customization. This multi-functional epitope approach allows a single vaccine formulation to serve multiple HLA types, resolving the contradiction between personalized effectiveness and manufacturing scalability
2Reliability
If current checkpoint inhibitor immunotherapies are used to re-activate existing immune responses, then clinical benefit is achieved for a fraction of patients, but the applicability to large populations deteriorates
Solution Approach 1:
The patent employs cancer testis antigens (CTAs) as preliminary action to induce new immune responses before tumor challenge. By pre-priming the immune system with CTA-based vaccines that target multiple HLA molecules, the invention creates a foundational immune response that can be subsequently enhanced, thereby expanding population applicability beyond what checkpoint inhibitors alone can achieve
3Reliability
If current cancer vaccines are designed to induce new immune responses, then the goal of prevention is addressed, but the immunogenicity and patient benefit deteriorate
Solution Approach 1:
The patent changes the key parameter of epitope selection criteria from HLA-restricted (binding to single HLA molecules) to multi-HLA binding (binding to at least three class I HLA molecules). This parameter change in epitope design dramatically improves immunogenicity across diverse populations while maintaining manufacturing simplicity, as the same multi-HLA binding epitopes can be used in standardized vaccine formulations without requiring complex individualized production
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 use of these polypeptides and compositions triggers immune responses in a broader population, potentially leading to effective prevention and treatment of breast, ovarian, and colorectal cancers by targeting multiple HLA molecules, thereby overcoming the limitations of existing vaccines.
Implementation Method 1
The fragments of a polypeptide antigen that are immunogenic for a specific individual are those that can bind to multiple class I (activate cytotoxic T cells) or class II (activate helper T cells) HLAs expressed by that individual
Data Source
AI summary
The disclosure relates to polypeptides and pharmaceutical compositions comprising polypeptides that find use in the prevention or treatment of cancer, in particular breast cancer, ovarian cancer and colorectal cancer. The disclosure also relates to methods of inducing a cytotoxic T cell response in a subject or treating cancer by administering pharmaceutical compositions comprising the peptides, and companion diagnostic methods of identifying subjects for treatment. The peptides comprise T cell epitopes that are immunogenic in a high percentage of patients.