T Cell Antigen Delivery via Constriction
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Solution Overview
Problem
Current methods for inducing endogenous T cell responses face challenges in effectively targeting and destroying diseased cells, particularly in stimulating CD8+ cytotoxic T lymphocytes and CD4+ helper T cells using disease-associated antigens.
Innovation Solution
Modified T cells are created by passing input T cells through a cell-deforming constriction to allow the introduction of exogenous antigens and adjuvants, such as CpG oligodeoxynucleotides, which are then incubated to facilitate their entry and presence within the T cells, enhancing their ability to modulate an immune response.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If T cells are stimulated with disease-associated antigens using current methods, then T cell responses are induced, but the effectiveness in targeting and destroying diseased cells is insufficient
Solution Approach 1:
The patent introduces a dual-component system where antigen-presenting cells are loaded with both antigen and adjuvant, creating a nested structure where the adjuvant is delivered intracellularly alongside the antigen. This nested approach enhances the reliability of T cell activation by ensuring co-delivery of both components to the same target cells, thereby improving the effectiveness of the immune response.
Solution Approach 2:
The patent uses antigen-presenting cells as intermediaries to deliver both antigen and adjuvant to target cells. These intermediary cells facilitate the transfer of immune-stimulating components, enabling effective T cell activation without requiring direct injection of antigens and adjuvants into T cells, thus improving ease of manufacture while maintaining reliability.
2Quantity of substance
If exogenous antigens and adjuvants are introduced into T cells through cell-deforming constriction, then intracellular presence is achieved, but cell structure is perturbed
Solution Approach 1:
The patent applies preliminary action by pre-loading antigen and adjuvant into antigen-presenting cells before they interact with T cells. This allows the immune components to be prepared in advance and delivered in a controlled manner, achieving intracellular presence without requiring direct mechanical perturbation of T cell structures during the actual immune activation process.
Solution Approach 2:
The patent replaces the mechanical cell-deforming constriction method with a biochemical approach where antigen-presenting cells naturally present antigens and deliver adjuvants to T cells through immune synapses. This substitution eliminates the need for physical deformation of T cells while still achieving effective intracellular delivery of immune-stimulating components.
Data Source
AI summary
The present application provides T cells comprising an antigen and an adjuvant, methods of manufacturing such T cells, and methods of using such T cells, such as for modulating an immune response in an individual.