HPV Immunogen Particle-Mediated T-Cell Expansion via MHC I/II
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Solution Overview
Problem
Current immunotherapies for HPV-positive cancers face challenges in effectively modulating the immune response, require invasive procedures for obtaining antigen-specific T-cells, and have limitations in safety and selectivity, particularly for solid cancers.
Innovation Solution
A method for expanding HPV immunogen-specific T-cells using phagocytosable particles containing HPV immunogens, such as those from Gardasil® or Cervarix®, which are internalized by APCs, processed, and presented via both MHC class I and II pathways, activating both CD4+ and CD8+ T-cells, and administered to patients to treat HPV-positive cancers.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current immunotherapy methods are used for HPV-positive cancers, then treatment approaches are available, but the immune response modulation is ineffective and safety/selectivity are limited
Solution Approach 1:
The patent uses phagocytosable particles as intermediaries to deliver HPV immunogens to antigen-presenting cells. These particles act as a mediator between the immunogen and the immune system, enabling effective presentation through both MHC class I and II pathways while maintaining safety and selectivity for HPV-positive cancers
Solution Approach 2:
The patent segments the immune response activation by using separate phagocytosable particle formulations that can selectively target different T-cell pathways. This allows independent optimization of CD4+ and CD8+ T-cell activation, improving overall effectiveness while maintaining safety through controlled delivery
2Quantity of substance
If invasive surgical procedures are used to obtain antigen-specific T-cells, then T-cell sources are obtained, but the procedures are invasive and the cells obtained are few and frequently unresponsive
Solution Approach 1:
The patent enables the patient's own antigen-presenting cells to perform the work of presenting immunogens and activating T-cells in vitro. This self-service approach eliminates the need for invasive surgical procedures to obtain T-cells, as peripheral blood mononuclear cells can be used instead, while still generating sufficient numbers of responsive T-cells
Solution Approach 2:
The patent performs preliminary activation and expansion of T-cells in vitro using phagocytosable particles before administration to the patient. This preliminary action ensures that sufficient numbers of highly responsive T-cells are generated without requiring invasive procedures, as the activation occurs in a controlled laboratory setting
3Productivity
If T-cell expansion is performed using current methods, then T-cells are obtained, but the expansion is slow and sufficient quantities take a long time to obtain
Solution Approach 1:
The patent maintains continuous stimulation of T-cells in vitro by providing ongoing exposure to phagocytosable particles containing HPV immunogens. This continuous useful action drives sustained proliferation and expansion of antigen-specific T-cells, significantly increasing the speed of expansion compared to intermittent or single-dose approaches
Solution Approach 2:
The patent optimizes expansion parameters by controlling the concentration, composition, and presentation format of HPV immunogens on phagocytosable particles. By adjusting these parameters, the system achieves rapid and efficient T-cell expansion, reducing the time required to obtain sufficient quantities for therapeutic administration
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 method efficiently activates and expands HPV-specific T-cells, providing a long-lasting, targeted immune response with reduced side effects, effectively treating HPV-positive cancers by harnessing both CD4+ and CD8+ T-cell activation pathways.
Implementation Method 1
contacting the HPV immunogen or the phagocytosable particle comprising a core and a HPV immunogen with the APCs from step ii in vitro, and under conditions allowing phagocytosis of the HPV immunogen by the APCs
Data Source
AI summary
The present invention provides a method for the expansion of HPV immunogen specific T cells, comprising the steps of: i. providing a phagocytosable particle comprising a core and a human papillomavirus (HPV) immunogen tightly associated to the core; wherein the HPV immunogen has an amino acid sequence that corresponds to the amino acid sequence of a HPV protein, or has an amino acid sequence that corresponds to an amino acid sequence of a part of a HPV protein; ii. providing APCs; iii. contacting the phagocytosable particle comprising a core and a HPV immunogen with the APCs from step ii in vitro, and under conditions allowing phagocytosis of the HPV immunogen by the APCs; iv. providing T-cells that have been harvested from a subject; v. contacting the T-cells with the APCs from step iii) in vitro, and under conditions allowing specific activation of HPV immunogen specific T-cells. The invention further provides an expanded population of therapeutically useful T-cells and their use in the treatment or prevention of cancer, particularly HPV positive cancers.