Researchers at the University of British Columbia (UBC) have demonstrated a method for producing human helper T cells from stem cells in a controlled laboratory environment.
The findings, published in Cell Stem Cell, address a limitation in the development and manufacturing of cell therapies. This development may influence the accessibility and cost-effectiveness of treatments for conditions such as cancer, infectious diseases, and autoimmune disorders.
Engineered cell therapies, such as CAR-T treatments for cancer, utilize reprogrammed human immune cells. These therapies have been applied in the treatment of diseases. Cell therapies are currently characterized by high cost, manufacturing complexity, and limited patient accessibility. This is primarily due to the current practice of manufacturing treatments from individual patient immune cells, which necessitates customized production processes.
The objective is to develop off-the-shelf cell therapies manufactured from renewable sources like stem cells. This approach aims to reduce treatment costs and improve availability.
Effective cell therapies for cancer typically involve both killer T cells, which target infected or cancerous cells, and helper T cells, which facilitate immune responses by activating other immune cells. Previous research had achieved stem cell-generated killer T cells, but consistent production of helper T cells had not been established.
In this study, UBC researchers identified a method to control the differentiation of stem cells into helper or killer T cells. The team determined that the developmental signal Notch plays a time-sensitive role. While Notch activity is required early in immune cell development, its prolonged activity prevents helper T cell formation.
By modulating the timing and extent of Notch signal reduction, researchers directed stem cells to develop into either helper or killer T cells. This process was conducted under laboratory conditions that are applicable to biomanufacturing.
The lab-grown helper T cells exhibited characteristics of mature immune cells. They displayed markers of healthy cells, possessed a diverse range of immune receptors, and could specialize into distinct immune subtypes.
The capacity to generate both helper and killer T cells, and to regulate their proportions, is noted as a factor that may influence the efficacy of future stem cell-derived immune therapies.
This technology provides a foundation for investigating the role of helper T cells in cancer cell elimination and for generating other T cell-derived cells, such as regulatory T cells, for clinical applications.