Allogeneic Dendritic Cell Feeder for T-Cell Expansion
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods for producing activated T cells for immunotherapy are inefficient and time-consuming, particularly in treating lymphocytopenia caused by viral infections, as they rely on autologous dendritic cells that can be damaging and require lengthy production processes, leading to variability in cell properties and low proportions of central memory phenotype cells.
Innovation Solution
The use of allogeneic mature dendritic cells as feeder cells in the early stages of T cell culture, which can be produced and cryopreserved in advance, significantly shortening the process to 7 days and enhancing T cell proliferation and activation, resulting in a higher proportion of CD4+ and CD8+ T cells that are predominantly autologous and safe for infusion.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If autologous dendritic cells are used for T cell expansion, then the process is safer for the patient, but the production time is extended and cell variability increases
Solution Approach 1:
Allogeneic dendritic cells are produced and cryopreserved in advance before the T cell expansion process begins. This preliminary preparation eliminates the time-consuming step of generating dendritic cells from the patient's own monocytes during the treatment process, thereby reducing overall production time while maintaining the safety of using autologous T cells for infusion.
Solution Approach 2:
Instead of using the patient's own dendritic cells (autologous), the invention uses dendritic cells from a different individual (allogeneic) as a substitute. These allogeneic dendritic cells serve as a temporary copy or surrogate to stimulate T cell expansion ex vivo, after which the expanded autologous T cells are infused back to the patient, combining the benefits of rapid production with patient-specific safety.
2Ease of manufacture
If conventional expansion protocols are used, then the process is simpler to implement, but the proportion of central memory phenotype cells is low and cell properties show high variability
Solution Approach 1:
Allogeneic dendritic cells are introduced as an intermediary component to mediate T cell stimulation and expansion. These dendritic cells express standardized costimulatory molecules (CD80, CD86, CD40) that provide consistent signals for T cell activation, leading to more uniform T cell properties and higher proportions of central memory phenotype cells compared to conventional protocols without such standardized intermediaries.
3Productivity
If rapid T cell production is prioritized, then treatment of lymphocytopenia is more effective, but the quality and activation state of T cells may be compromised
Solution Approach 1:
The allogeneic dendritic cells are prepared in advance and cryopreserved, allowing the actual T cell expansion process to begin immediately upon receiving the patient's T cells. This preliminary preparation enables rapid production without compromising the activation state, as the pre-prepared dendritic cells are ready to provide immediate stimulatory signals upon thawing and co-culture with the patient's T cells.
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 approach allows for the rapid production of pharmaceutically acceptable and immunotherapeutically effective T cells, increasing CD4+ T cell numbers and mobilizing endogenous T cells, effectively treating lymphocytopenia and potentially severe viral infections like COVID-19, with a reduced risk of adverse immune responses.
Implementation Method 1
mixing mononuclear cells from a human subject with mature allogeneic human dendritic cells; co-culturing the mixed cells from step a) under conditions that stimulate proliferation of CD4+ and CD8+ T lymphocytes
Implementation Method 2
co-culturing the mixed cells from step a) under conditions that stimulate proliferation of CD4+ and CD8+ T lymphocytes, whereby the lymphocyte number is increased and the lymphocyte phenotypes are altered
Implementation Method 3
which can be produced and cryopreserved in advance
Data Source
AI summary
Provided is a method for preparation of a composition comprising activated human CD4+ and CD8+ lymphocytes. The method entails use of allogeneic mature dendritic cells as feeder cells added at an early stage in the induction of proliferation and activation of CD4+ and CD8+ T cells. Further provided is a method for treatment of lymphopenia related diseases by infusion of the cells obtained from the present process.