HPV E6 Epitope Selection via T Cell Response Magnitude
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Solution Overview
Problem
Current methods are inadequate in identifying and utilizing peptide antigens from the Human Papilloma virus (HPV) E6 protein for therapeutic vaccines or dendritic cell immunotherapy to treat cervical cancer, as they do not select epitopes based on the magnitude of T cell responses.
Innovation Solution
A method involving pulsing dendritic cells with recombinant HPV proteins to stimulate T cell lines, identifying peptides that induce T cell responses, and using these peptides to generate immunotherapy by transferring immune cells back to patients to activate specific immune responses against HPV epitopes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If current methods are used to identify peptide antigens from HPV E6 protein, then the process can be completed, but the epitopes cannot be selected based on the magnitude of T cell responses
Solution Approach 1:
The patent employs feedback mechanisms by measuring T cell responses to peptide pools and using this information to iteratively identify and select immunodominant epitopes. The method involves stimulating T cells with overlapping peptide pools, measuring interferon-gamma secretion, and using these response data to feedback-select the most potent epitopes for therapeutic vaccine development.
Solution Approach 2:
The patent changes the parameter of epitope selection criteria from arbitrary or binding-based selection to magnitude-based selection using measurable T cell response parameters. By quantifying T cell responses through interferon-gamma secretion assays and selecting epitopes based on the magnitude of response rather than just binding affinity, the method achieves both measurement precision and therapeutic effectiveness.
2Reliability
If peptides are used to generate immunotherapy, then specific immune responses can be activated, but the process complexity increases
Solution Approach 1:
The patent segments the HPV E6 protein into overlapping peptide pools covering the entire protein sequence. This segmentation allows systematic evaluation of different epitope regions and enables the identification of immunodominant epitopes through measured T cell responses. The segmented approach makes the complex immunotherapy process more manageable and reliable.
Solution Approach 2:
The patent uses dendritic cells as intermediary antigen-presenting cells to stimulate T cell responses in vitro. These dendritic cells serve as mediators that process and present peptide antigens to T cells, enabling the generation of specific immune responses without directly administering complex viral proteins to patients. This intermediary approach simplifies the therapeutic process while maintaining specificity.
3Productivity
If CD8 T cell responses are generated against HPV epitopes, then cervical lesions can regress, but the identification process is time-consuming
Solution Approach 1:
The patent performs preliminary actions by identifying and characterizing immunodominant epitopes in vitro before administering therapeutic vaccines to patients. Through preliminary T cell stimulation and interferon-gamma measurement assays, the most effective epitopes are selected in advance, which accelerates the subsequent therapeutic process and increases lesion regression rates without extending overall treatment time.
Data Source
AI summary
The present invention is directed to the examination of the pattern of immunodominant T cell epitopes in the E6 protein of Human Papilloma virus and its further characterization in terms of its amino acid sequence and Human Leukocyte Antigen restriction. These epitopes are identified based on their ability to induce specific T cell responses and therefore, are important as sources of antigens for immunotherapies to treat cervical and other cancers. The present invention contemplates identifying a number of similar epitopes restricted by a wide variety of Human Leukocyte Antigen types so that they can be used together to develop preventative or therapeutic vaccines, which can be used for the general human population.