Researchers at the University of Pittsburgh have discovered a groundbreaking method to grow T cells in the lab that not only extends their lifespan but also improves their ability to target and destroy cancer cells. This innovative technique, tested in a mouse model of melanoma, could significantly enhance the success of cancer immunotherapy that involves expanding T cells outside the body and reinfusing them into patients.
The findings, published in Cell Metabolism, highlight the potential to revolutionize T cell-based therapies, such as CAR-T and TIL therapies, by creating T cells that can survive longer and function more effectively once reintroduced into the patient.
Traditional Methods Fall Short
T cells are critical players in the immune system, helping fight infections and cancer. In current cancer immunotherapy, T cells are extracted from patients, grown in large numbers in the lab, and then reinfused to help fight tumours. However, the process is inefficient, with many of the T cells dying before they can be effective.
“Our traditional methods of growing T cells are horribly inefficient,” said Greg Delgoffe, senior author of the study and professor of Immunology at Pitt’s School of Medicine. “We make millions of T cells, but most of them die before they can make an impact. Our research is focused on finding new ways to produce T cells that live longer and are more effective in fighting cancer.”
Revolutionizing T Cell Growth
The research team, led by graduate student Andrew Frisch, identified a major issue with how T cells are grown in the lab. Traditional growth media is overly rich in glucose, which leads T cells to become dependent on this sugar for energy. However, when these sugar-dependent cells are reintroduced into the body, they struggle to survive on the other energy sources available in the bloodstream, causing many of them to perish quickly.
To address this, Delgoffe and his team introduced a compound called dichloroacetate (DCA) into the growth medium. DCA alters the metabolism of T cells, making them less reliant on glucose and better able to utilize other energy sources found in the body.
Promising Results in Mouse Models
The team’s new approach showed remarkable results in a mouse model of melanoma. T cells grown with DCA lived significantly longer than those grown in traditional media. Even nearly a year later, more than 5% of the transferred T cells were still present in the mice, compared to almost no detectable cells in the control group. In addition, the mice treated with DCA-grown T cells showed better control of their tumours and had a significantly higher survival rate.
“By limiting access to certain nutrients, we trained the T cells to become more adaptable, enabling them to thrive in the body’s natural environment,” said Delgoffe. “The ultimate goal is to create T cells that can stay on guard, providing long-lasting protection against cancer, just like how the chicken pox vaccine provides lifelong immunity.”
Long-Term Potential for Cancer Immunotherapy
The success of this approach opens the door to enhancing existing cancer immunotherapy. With improved T cell longevity and effectiveness, these therapies could offer more durable and long-lasting cancer treatment options. The findings also suggest that this new method could eventually enable T cells to be “on guard” indefinitely, providing a lasting defence against cancer recurrence.
As cancer immunotherapy continues to evolve, these advancements could lead to more effective treatments, ultimately offering patients better chances of survival and a higher quality of life.
