UBC Researchers Achieve Milestone in Stem Cell-Derived Immunotherapy

Researchers at the University of British Columbia have made a significant breakthrough in stem cell engineering by demonstrating the reliable production of human immune cells known as helper T cells. This advancement, detailed in a study published in Cell Stem Cell, addresses a major barrier to developing and manufacturing cell therapies, which could lead to more accessible treatments for conditions such as cancer and autoimmune disorders.

The study, co-led by Dr. Peter Zandstra, a professor and director of the UBC School of Biomedical Engineering, highlights the potential for engineered cell therapies to transform medical treatment. “This study addresses one of the biggest challenges in making these lifesaving treatments accessible to more people,” he stated, emphasizing the importance of scalable production methods.

In recent years, therapies like CAR-T have shown remarkable success in treating cancer by reprogramming immune cells to combat disease. Despite their efficacy, these treatments are often costly and complex, primarily because they require the use of a patient’s own cells, leading to long wait times for customized manufacturing.

The long-term vision, according to co-senior author Dr. Megan Levings, is to create off-the-shelf therapies that can be produced in advance from renewable sources like stem cells. “This would make treatments much more cost-effective and ready when patients need them,” she explained.

For effective cancer treatment, both killer T cells and helper T cells are essential. While the production of killer T cells from stem cells has progressed, generating helper T cells has remained a challenge. “Helper T cells are crucial for a strong and lasting immune response,” Dr. Levings noted, underlining the need for both cell types in therapy.

Unlocking Stem Cell Potential

The researchers overcame this challenge by fine-tuning biological signals during cell development, specifically focusing on a signal known as Notch. This signal is critical in the early stages but must be carefully regulated; prolonged Notch activity can inhibit the formation of helper T cells.

By adjusting the timing and intensity of Notch signaling, the team successfully directed stem cells to develop into either helper or killer T cells. Dr. Ross Jones, a research associate in the Zandstra Lab, remarked, “This essential step toward turning this discovery into a viable therapy demonstrates our ability to control stem cell fate in a laboratory setting that mirrors real-world biomanufacturing processes.”

The laboratory-grown helper T cells exhibited characteristics of mature immune cells, demonstrating diversity in immune receptors and the ability to specialize into various subtypes. PhD student Kevin Salim highlighted the significance of these findings, stating, “These cells look and act like genuine human helper T cells. That’s critical for future therapeutic potential.”

The ability to generate a balanced population of both helper and killer T cells is expected to enhance the efficacy of future stem cell-based therapies.

Implications for Future Therapies

Dr. Zandstra emphasized the broader implications of this research, stating, “This is a major step forward in our ability to develop scalable and affordable immune cell therapies.” The findings lay the groundwork for further investigations into the role of helper T cells in cancer elimination and the creation of new regulatory T cells for clinical applications.

As researchers continue to refine these techniques, the prospect of off-the-shelf cell therapies may soon become reality, potentially transforming the landscape of treatment for various diseases. This breakthrough signifies a pivotal moment in the quest for more effective and accessible medical therapies derived from stem cells.