Specialized Immune Cells Grown in Labs Offer Hope for Autoimmune Patients

Researchers at the University of British Columbia (UBC) have made a significant discovery regarding the cultivation of specialized immune cells, which facilitates the development of readily available, off-the-shelf cell therapies aimed at treating cancer, autoimmune diseases, and other conditions.

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The scientists have successfully shown how to consistently generate a crucial type of human immune cell, helper T cells,  from stem cells within a regulated laboratory environment.

The study, published in Cell Stem Cell, addresses a significant obstacle that has hindered the advancement, cost-effectiveness, and mass production of cell therapies. This breakthrough may lead to more readily available and efficient off-the-shelf treatments for various conditions, including cancer, infectious diseases, autoimmune disorders, and beyond.

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, Study Co-Senior Author, Professor and Director, School of Biomedical Engineering, University of British Columbia (UBC)

The Promise and Challenge of Living Drugs

In recent years, engineered cell therapies, including CAR-T treatments for cancer, have provided remarkable and life-saving outcomes for patients suffering from otherwise untreatable diseases. These therapies function by reprogramming human immune cells to identify and combat illness, effectively transforming the cells into ‘living drugs.’

Cell therapies continue to be costly, complicated to produce, and unavailable to patients worldwide. A primary factor contributing to this is that the majority of current treatments are derived from a patient’s own immune cells, necessitating weeks of tailored manufacturing for each individual 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. This would make treatments much more cost-effective and ready when patients need them.

Dr. Megan Levings, Study Co-Senior Author and Professor, Surgery and Biomedical Engineering, University of British Columbia (UBC)

Cancer cell therapies are most effective when two varieties of immune cells are available: killer T cells, which directly assault infected or malignant cells, and helper T cells, which function as the conductors of the immune system, identifying health threats, activating additional immune cells, and maintaining immune responses over time.

Despite advancements in utilizing stem cells to create killer T cells in laboratory settings, researchers have yet to generate helper T cells consistently.

“Helper T cells are essential for a strong and lasting immune response. It’s critical that we have both to maximize the efficacy and flexibility of off-the-shelf therapies,” said Dr. Levings

UBC research associate Dr. Ross Jones in the lab where they are working to develop cell-based therapies from stem cells. Image Credit: Phillip Chin

A Big Step toward Stem Cell-Grown Therapies

The researchers have successfully addressed a longstanding issue, modifying essential biological signals during cell development to accurately determine whether stem cells differentiate into helper or killer T cells.

The team found that a developmental signal known as Notch is crucial yet time-sensitive. Although Notch is necessary in the early stages of immune cell development, prolonged activation of this signal hinders 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. 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,” said Dr. Ross Jones, Study Co-First Author and Research Associate, Zandstra Lab, University of British Columbia (UBC).

Crucially, the researchers illustrated that the laboratory-cultivated helper T cells not only resembled authentic immune cells but also exhibited similar behaviors. These cells displayed characteristics of healthy mature cells, possessed a wide variety of immune receptors, and had the capability to differentiate into subtypes that fulfill specific functions in the immune response.

These cells look and act like genuine human helper T cells. That’s critical for future therapeutic potential.

Kevin Salim, Study Co-First Author and Ph.D. Student, University of British Columbia (UBC)

The researchers assert that the capacity to produce both helper and killer T cells, as well as to regulate the equilibrium between them, will greatly enhance the effectiveness of immune therapies developed from stem cells in the future.

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