For the first time, researchers at the University of British Columbia (UBC) have successfully produced human helper T cells from stem cells in a laboratory setting. The findings, published in Cell Stem Cell, address a significant barrier that has limited the development and scalability of cell therapies.
Cell therapies, including CAR-T treatments for cancer, have shown strong results for patients with otherwise untreatable diseases. These therapies involve reprogramming immune cells to target and attack illness. However, most current approaches require using each patient's own immune cells, leading to high costs and lengthy production times.
Dr. Megan Levings, co-senior author and professor of surgery and biomedical engineering at UBC, explained: "The long-term goal is to have off-the-shelf cell therapies that are manufactured ahead of time and on a larger scale from a renewable source like stem cells. This would make treatments much more cost-effective and ready when patients need them."
Effective cell therapies often require both killer T cells—cells that directly destroy infected or cancerous cells—and helper T cells, which coordinate immune responses. While scientists have been able to create killer T cells from stem cells in the lab, reliably producing helper T cells has remained challenging until now.
"Helper T cells are essential for a strong and lasting immune response," said Dr. Levings. "It's critical that we have both to maximize the efficacy and flexibility of off-the-shelf therapies."
The UBC research team overcame this challenge by adjusting biological signals during cell development to control whether stem cells became helper or killer T cells. They found that the Notch developmental signal plays an important but time-sensitive role; if active too long, it blocks the formation of helper T cells.
"By precisely tuning when and how much this signal is reduced, we were able to direct stem cells to become either helper or killer T cells," said Dr. Ross Jones, co-first author and research associate in the Zandstra Lab. "We were able to do this in controlled laboratory conditions that are directly applicable in real-world biomanufacturing, which is an essential step toward turning this discovery into a viable therapy."
Tests showed that lab-grown helper T cells functioned similarly to those found naturally in humans—they displayed markers of maturity, had diverse immune receptors, and could develop into specialized subtypes needed for various immune functions.
"These cells look and act like genuine human helper T cells," said Kevin Salim, co-first author and PhD student in the Levings Lab. "That's critical for future therapeutic potential."
According to Dr. Peter Zandstra: "This is a major step forward in our ability to develop scalable and affordable immune cell therapies." He added: "This technology now forms the foundation for testing the role of helper T cells in supporting the elimination of cancer cells and generating new types of helper T cell-derived cells, such as regulatory T cells, for clinical applications."
