UBC researchers have figured out how to reliably grow a crucial kind of immune cell from stem cells. The advance could make powerful cell therapies cheaper, faster and more widely available.
For the first time, scientists have figured out how to reliably grow a key type of human immune cell from stem cells in the lab — a breakthrough that could help turn cutting-edge “living drugs” into treatments that are cheaper, faster and easier to access.
Researchers at the University of British Columbia report that they can now steer human stem cells to become either of two powerful immune cell types, known as helper T cells and killer T cells, in a controlled, scalable way. Their findings, published in the journal Cell Stem Cell, tackle one of the major bottlenecks in bringing engineered cell therapies to more patients.
Engineered cell therapies, including CAR-T treatments for cancer, work by reprogramming a patient’s own immune cells so they can recognize and destroy disease. These therapies have produced dramatic results for some people with otherwise untreatable cancers, earning them the nickname “living drugs.”
But today’s cell therapies are custom-made for each patient, using that person’s own immune cells. That means weeks of complex, individualized manufacturing, high costs and limited availability.
“Engineered cell therapies are transforming modern medicine,” co-senior author Peter Zandstra, a professor and director of the UBC School of Biomedical Engineering, said in a news release. “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.”
The long-term vision in the field is to move away from one-patient-at-a-time manufacturing and toward off-the-shelf products made in advance from renewable sources such as stem cells. Stem cells can, in principle, be grown in large quantities and then guided to become specific cell types on demand.
That is exactly the direction researchers are aiming for, noted co-senior author Megan Levings, a professor of surgery and biomedical engineering at UBC.
“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,” she said in the news release. “This would make treatments much more cost-effective and ready when patients need them.”
To get there, scientists need to be able to generate the right mix of immune cells. Cancer-fighting cell therapies work best when both killer T cells and helper T cells are present. Killer T cells directly attack infected or cancerous cells. Helper T cells act more like conductors, sensing threats, activating other immune cells and helping immune responses last.
While researchers have made progress turning stem cells into killer T cells, reliably producing helper T cells has remained out of reach.
“Helper T cells are essential for a strong and lasting immune response,” Levings added. “It’s critical that we have both to maximize the efficacy and flexibility of off-the-shelf therapies.”
In the new study, the UBC team uncovered how to solve this long-standing problem by carefully adjusting the biological signals that guide stem cells as they mature into immune cells.
They focused on a developmental signal called Notch, which is known to be important early in immune cell formation. The researchers discovered that while Notch is needed at the start, keeping this signal switched on for too long actually blocks helper T cells from forming.
By learning when and how to dial this signal up or down, the scientists could control the fate of the developing 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,” added co-first author 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.”
Just making cells that look like helper T cells under a microscope is not enough. They also have to behave like the real thing.
The team showed that their lab-grown helper T cells carried markers of healthy, mature cells and displayed a wide variety of immune receptors — the molecular “antennae” that allow T cells to recognize different threats. The cells could also specialize into different helper T cell subtypes that play distinct roles in the immune system.
“These cells look and act like genuine human helper T cells,” added co-first author Kevin Salim, a UBC doctoral student in the Levings Lab. “That’s critical for future therapeutic potential.”
Being able to generate both helper and killer T cells from stem cells — and to control the balance between them — could make future stem cell–derived therapies more powerful and more flexible. For example, researchers could design cell products tailored for different diseases, or adjust the ratio of helper to killer cells to fine-tune how strong and how long an immune response lasts.
“This is a major step forward in our ability to develop scalable and affordable immune cell therapies,” Zandstra 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.”
Regulatory T cells are another specialized immune cell type that helps keep the immune system in balance and prevent it from attacking the body’s own tissues. In the future, stem cell–derived regulatory T cells could be used to treat autoimmune diseases or to help transplanted organs be accepted by the body.
For now, the UBC team’s work is a key step toward that broader vision. By showing that stem cells can be reliably turned into both major T cell types in conditions suitable for large-scale manufacturing, they have brought the idea of off-the-shelf living drugs closer to reality.
If future studies confirm the safety and effectiveness of these lab-grown cells in animals and, eventually, in people, patients with cancer, infectious diseases and autoimmune disorders could one day receive powerful, pre-made immune cell therapies without the long wait or high price tag that come with today’s custom treatments.
Source: The University of British Columbia Faculty of Medicine