Scientists at the University of British Columbia report a method to consistently produce human helper T cells from pluripotent stem cells by carefully adjusting the timing of a developmental signal known as Notch. The work, published in Cell Stem Cell, is positioned as a step toward scalable “off-the-shelf” immune-cell therapies for cancer and other diseases.
For years, engineered cell therapies such as CAR-T have delivered dramatic results for some cancers by reprogramming a patient’s immune cells into targeted “living drugs.” But these treatments remain expensive and complex to manufacture, in part because many are made from a patient’s own cells and require weeks of individualized production.
Researchers at the University of British Columbia (UBC) say they have now overcome a long-standing obstacle to making stem cell–derived immune therapies more scalable: reliably generating human helper T cells from pluripotent stem cells in controlled laboratory conditions.
Helper T cells play a central coordinating role in immune responses, including detecting threats, activating other immune cells and helping sustain immune activity over time. UBC’s team says cancer cell therapies work best when helper T cells are present alongside killer (cytotoxic) T cells, which directly attack infected or cancerous cells. While researchers have made progress generating killer T cells from stem cells, reliably producing helper T cells has been difficult.
In the new study, the UBC group—co-led by Dr. Peter Zandstra and Dr. Megan Levings—reported that a developmental pathway known as Notch is essential early in T cell development but can block helper T cell formation if it stays active too long. By adjusting the timing and degree of Notch signaling, the researchers said they could steer stem cells toward becoming either helper (CD4) or killer (CD8) 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 co-first author Dr. Ross Jones, a research associate in the Zandstra Lab.
The team reported that the lab-grown helper T cells showed multiple hallmarks associated with functional immune cells, including markers of maturity, a diverse range of immune receptors and the ability to specialize into different helper T cell subtypes.
“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.
Researchers involved in the work said the longer-term aim is to support the development of pre-manufactured, “off-the-shelf” immune-cell therapies produced at larger scale from renewable sources such as stem cells.
“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,” Levings said.
Zandstra said the approach could provide a foundation for studying how helper T cells can support the elimination of cancer cells and for developing related immune-cell products, including regulatory T cells, for potential clinical applications.
The study was published in Cell Stem Cell on January 7, 2026, according to UBC and ScienceDaily summaries of the work.
