HPV-Specific T Cell Expansion From Naïve Donors Using Dendritic Cells
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods for generating antigen-specific T cells, particularly for HPV, from naïve donors are inefficient and require the use of live viruses or virus-transformed cells, posing regulatory and clinical risks, and are ineffective when memory T cells are not present or insufficient.
Innovation Solution
A method involving the cultivation of dendritic cells with specific cytokines and peptides to expand antigen-specific T cells from naïve donors, without the use of live viruses, using cytokines such as GM-CSF, IL-4, IL-6, IL-1β, TNF-α, PGE1, PGE2, and IL-15, and employing overlapping peptide libraries for HPV antigens like E6 and E7.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If memory T cells are used to generate antigen-specific T cells, then the expansion efficiency is high and the process is simple, but memory T cells are not present or insufficient in naïve donors
Solution Approach 1:
The patent applies preliminary action by using dendritic cells to pre-process and present antigen peptides to naïve T cells before expansion. The dendritic cells are pulsed with overlapping peptide libraries representing multiple HPV antigens, creating a primed environment that enables efficient expansion of antigen-specific T cells from naïve donors without requiring pre-existing memory T cells.
Solution Approach 2:
The patent uses dendritic cells as an intermediary between the antigen peptides and naïve T cells. The dendritic cells process and present the antigen peptides through MHC molecules, serving as a bridge that activates naïve T cells and enables their expansion into antigen-specific effector and memory T cells, thereby solving the problem of insufficient memory T cells in naïve donors.
2Reliability
If live viruses or virus-transformed cells are used to generate antigen-specific T cells, then the immunogenicity is high, but regulatory and clinical risks increase
Solution Approach 1:
The patent extracts the essential immunogenic component (antigen peptides) from the live virus or virus-transformed cells. By using overlapping peptide libraries that represent multiple HPV antigens, the invention isolates the protective epitopes without the harmful elements of live viruses, thereby maintaining immunogenicity while eliminating regulatory and clinical risks.
Solution Approach 2:
The patent uses synthetic peptide copies of viral antigens instead of live viruses. The overlapping peptide libraries contain synthetic peptides that replicate the antigenic structure and epitopes of HPV antigens, providing the necessary immunogenic stimulation to generate antigen-specific T cells without the risks associated with live viral materials.
3Ease of operation
If conventional methods are used to expand T cells from naïve donors, then the process is simple, but the expansion is ineffective when memory T cells are absent
Solution Approach 1:
The patent introduces dendritic cells as an intermediary to bridge the gap between simple culture conditions and effective expansion of naïve T cells. The dendritic cells, when pulsed with antigen peptides, create a localized immunogenic environment that selectively activates and expands antigen-specific naïve T cells without requiring complex culture protocols or pre-existing memory T cells.
Solution Approach 2:
The patent applies local quality by creating a localized antigen-presenting microenvironment using dendritic cells pulsed with specific peptide libraries. This localized presentation of antigens to naïve T cells within the culture system enables selective expansion of antigen-specific T cells while maintaining overall process simplicity, without requiring complex modifications to the entire culture system.
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
This method allows for the rapid and robust expansion of antigen-specific T cells, suitable for banking and off-the-shelf use, providing effective immune response against HPV and other pathogens, including HPV-associated malignancies, without the use of live viruses.
Implementation Method 1
culturing the first population of dendritic cells produced in (b) in a medium comprising peptides derived from at least one, two, three or more antigens of interest
Implementation Method 2
culturing the antigen-specific T cell population from step (e) with a second population of dendritic cells in a medium comprising IL-7 and IL-15
Data Source
AI summary
Safe, rapid, and efficient methods for producing antigen-specific T cells recognizing human papilloma virus (HPV antigens); HPV-specific T cells, and methods for treating HPV infections and HPV-related malignancies by adoptive transfer of HPV-specific T cells.