UBC researchers crack code to grow helper t cells from stem cells

For the first time, researchers at the University of British Columbia have demonstrated how to reliably produce an important type of human immune cell-known as helper T cells-from stem cells in a controlled laboratory setting. 

The findings, published today in Cell Stem Cell, overcome a major hurdle that has limited the development, affordability and large-scale manufacturing of cell therapies. The discovery could pave the way for more accessible and effective off-the-shelf treatments for a wide range of conditions like cancer, infectious diseases, autoimmune disorders and more. 

Engineered cell therapies are transforming modern medicine, This study addresses one of the biggest challenges in making these lifesaving treatments accessible to more people, showing for the first time a reliable and scalable way to grow multiple immune cell types." 

Dr. Peter Zandstra, co-senior author, professor and director of the UBC School of Biomedical Engineering

The promise and challenge of living drugs 

In recent years, engineered cell therapies, such as CAR-T treatments for cancer, have delivered dramatic and lifesaving results for patients with otherwise untreatable disease. These therapies work by reprogramming human immune cells to recognize and attack illness, essentially turning the cells into 'living drugs'. 

Despite their tremendous promise, cell therapies remain expensive, complex to produce and inaccessible to many patients worldwide. One major reason is that most current treatments are made from a patient's own immune cells, requiring weeks of customized manufacturing for each patient. 

"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," said co-senior author Dr. Megan Levings, a professor of surgery and biomedical engineering at UBC. "This would make treatments much more cost-effective and ready when patients need them." 

Cell therapies for cancer work best when two types of immune cell are present: killer T cells, which directly attack infected or cancerous cells, and helper T cells, which act as the immune system's conductors-detecting health threats, activating other immune cells and sustaining the immune responses over time. 

Although progress has been made using stem cells to generate killer T cells in the lab, scientists have so far been unable to reliably produce helper T cells. 

"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." 

A big step toward stem cell-grown therapies 

In the new study, the UBC researchers were able to solve this long-standing challenge-adjusting key biological signals during cell development to precisely control whether stem cells developed into either helper or killer T cells. 

The team discovered that a developmental signal called Notch plays a critical but time-sensitive role. While Notch is needed early in immune cell development, if the signal remains active for too long, it prevents helper T cells from forming. 

"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 co-first author Dr. Ross Jones, a 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." 

Importantly, the researchers demonstrated that the lab-grown helper T cells didn't just resemble real immune cells-they behaved like them. The cells showed markers of healthy mature cells, carried a diverse range of immune receptors and could specialize into subtypes that play distinct roles in immunity. 

"These cells look and act like genuine human helper T cells," said co-first author Kevin Salim, a UBC PhD student in the Levings Lab. "That's critical for future therapeutic potential." 

The researchers say the ability to generate both helper and killer T cells-and to control the balance between them-will significantly improve the efficacy of stem cell-grown immune therapies in the future. 

"This is a major step forward in our ability to develop scalable and affordable immune cell therapies," said Dr. Zandstra. "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."