Antigen-Specific T Cell Expansion via Segmented Co-Culture
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods for generating T cells for cancer immunotherapy do not effectively increase the dose of antigen-specific T cells, which are necessary for targeted cancer therapies, as they primarily focus on non-specific expansion, rendering them unsuitable for therapies requiring antigen-specificity.
Innovation Solution
A method involving an antigen-specific expansion step followed by a non-specific boost expansion step, utilizing co-culture with antigen-presenting cells loaded with antigen and cytokines like IL-2, anti-CD3, anti-CD28, and anti-CD2 antibodies to enhance the number and functionality of antigen-specific T cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If non-specific expansion methods are used to generate large numbers of T cells, then the total T cell dose is increased, but the proportion of antigen-specific T cells does not increase
Solution Approach 1:
The expansion process is divided into distinct phases: an initial antigen-specific expansion phase using antigen-presenting cells to enrich antigen-specific T cells, followed by a non-specific boost expansion phase to amplify the enriched population. This segmentation allows each phase to optimize for its specific function, resolving the contradiction between total dose and antigen-specificity.
Solution Approach 2:
The antigen-specific expansion step is performed as a preliminary action before the main non-specific expansion. This preliminary enrichment of antigen-specific T cells ensures that when the subsequent boost expansion occurs, it amplifies a population that already has the desired antigen-specificity, rather than trying to achieve specificity during the expansion itself.
2Manufacturing precision
If antigen-specific expansion is performed to increase antigen-specific T cell proportion, then antigen-specificity is improved, but the total number of T cells produced is limited
Solution Approach 1:
The invention merges two previously separate approaches (antigen-specific expansion and non-specific boost expansion) into a unified two-step process. The antigen-specific expansion establishes the desired specificity, while the subsequent non-specific boost expansion multiplies the total cell number. By combining these approaches sequentially, both antigen-specificity and total dose requirements are satisfied.
3Manufacturing precision
If multiple expansion steps are implemented to increase antigen-specific T cells, then antigen-specificity and dose are improved, but the process complexity increases
Solution Approach 1:
The invention uses defined intermediary reagents (specific cytokines, antibodies, and antigen-presenting cells) to mediate each expansion step. These standardized intermediaries simplify the control and optimization of each phase, making the multi-step process more manageable and reproducible despite the increased number of steps.
Data Source
AI summary
The present invention relates to a method for producing antigen-specific T cells and their use in a method for the treatment or prevention of cancer.