HPV-Specific T Cell Expansion From Naive Donors Using Peptide Libraries
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Solution Overview
Problem
Current methods struggle to effectively expand HPV-specific T cells from naive donors due to the absence of memory T cells, posing challenges for treating HPV infections and associated malignancies, and existing approaches using viruses or virus-transformed cells are undesirable due to clinical risks and regulatory hurdles.
Innovation Solution
A method using overlapping peptide libraries pulsed onto antigen-presenting cells, combined with specific cytokines and selection methods, to generate HPV-specific T cells from naive T cells without live viruses, enabling robust expansion and storage for therapeutic use.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If viruses or virus-transformed cells are used to expand antigen-specific T cells, then T cell expansion is achieved, but clinical risks and regulatory hurdles increase
Solution Approach 1:
The patent extracts the essential antigenic components from viruses by using peptide libraries that represent viral epitopes. Instead of using whole viruses or virus-transformed cells, the invention isolates and uses only the relevant peptide sequences to stimulate T cell expansion, thereby achieving T cell proliferation without the safety risks associated with live viral materials
Solution Approach 2:
The patent creates simplified copies of viral antigens in the form of peptide libraries. These peptide copies contain the essential epitopic information needed to activate antigen-specific T cells but lack the pathogenic properties of the original viruses. This copying approach enables safe T cell expansion by using representative rather than authentic viral materials
2Object-affected harmful factors
If peptide-based methods are used to expand antigen-specific T cells from naive donors, then clinical safety is improved, but expansion success is limited
Solution Approach 1:
The patent segments the antigen recognition process into multiple discrete peptide components organized in libraries. By dividing the complex antigen structure into overlapping peptide fragments that can be systematically presented to naive T cells, the invention enables stepwise activation and expansion of antigen-specific clones without requiring pre-existing memory cells
Solution Approach 2:
The patent creates a universal peptide library system that can be applied to expand T cells specific for multiple different viral antigens using the same platform. The overlapping peptide design and standardized presentation method provide a multi-functional approach that works across different viral targets, enhancing productivity while maintaining safety
3Productivity
If autologous cells from previously exposed patients are used, then HPV-specific T cell generation is successful, but applicability to healthy donors and third party banking is limited
Solution Approach 1:
The patent prepares comprehensive peptide libraries covering multiple HPV antigen types in advance, enabling direct priming of naive T cells from unexposed donors. This preliminary preparation of antigenic stimuli eliminates the need to wait for in vivo exposure or pre-existing immunity, allowing immediate activation and expansion of HPV-specific T cell clones from any donor including healthy individuals
Solution Approach 2:
The patent inverts the traditional approach by not requiring the donor to have been exposed to HPV antigens. Instead of relying on the donor's immune history, the invention actively induces antigen-specific T cell responses de novo using peptide libraries, thereby enabling application to healthy donors and third-party banking scenarios
Data Source
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AI summary
Safe, rapid and efficient methods for producing antigen-specific T cells recognizing human papilloma virus or HPV antigens.