Artificial Antigen-Presenting Cell for T Cell Expansion
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Solution Overview
Problem
Current methods for generating and expanding antigen-specific T cells in vitro are limited by the availability of dendritic cells and feeder cells, and there is uncertainty about the optimal combinations of co-stimulatory ligands required for T cell stimulation, often leading to over-stimulation and difficulty in expanding exhausted T cells.
Innovation Solution
An artificial antigen-presenting cell (aAPC) comprising immune stimulatory ligands CD86, CD70, and CD137L is used to induce proliferation and expansion of immune cells, which can be engineered to express specific antigens and modify binding affinity to CD8 for enhanced T cell activation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If dendritic cells or feeder cells are used to generate antigen-specific T cells, then T cell generation is achieved, but the availability and quantity of T cells are limited due to limited availability of dendritic cells and feeder cells
Solution Approach 1:
The patent creates artificial antigen-presenting cells (aAPCs) that copy the essential functions of natural dendritic cells and feeder cells. These aAPCs present peptide/HLA complexes and express immunostimulatory molecules to mimic the behavior of natural APCs, thereby providing an unlimited source for T cell expansion without being constrained by the availability of donor-derived dendritic cells
Solution Approach 2:
The aAPCs are designed to perform multiple functions: they present antigens via peptide/HLA complexes, provide co-stimulatory signals through molecules like CD80, CD86, and CD137L, and can be used for both generation and expansion of antigen-specific T cells. This multi-functionality replaces the need for multiple different cell types (dendritic cells and feeder cells) with a single universal platform
2Productivity
If combinations of co-stimulatory ligands are used to stimulate T cells, then T cell proliferation is enhanced, but uncertainty about optimal combinations leads to over-stimulation and exhausted immunophenotype
Solution Approach 1:
The patent systematically varies the parameters of co-stimulatory ligand combinations (CD80, CD86, CD137L) to identify optimal conditions for T cell expansion. By controlling the presence, absence, and relative proportions of different co-stimulatory molecules, the invention finds the right balance that promotes proliferation without causing over-stimulation or exhaustion, thereby converting an uncertain parameter space into a controlled optimization process
Data Source
AI summary
The invention relates to an artificial antigen-presenting cell (aAPC) comprising at least one immune stimulatory ligand and co-stimulatory ligands comprising or consisting of CD86, CD70 and CD137L, methods of preparing an aAPC and methods of inducing proliferation of an immune cell or expanding a population of immune cells. The invention also relates to methods for inducing an immune response or treating a medical condition in a subject. The invention further relates to methods of identifying an antigenic peptide or method of identifying or detecting the presence of an immune cell that recognizes an antigen.