Investigator Weiguo Cui, MD, PhD, believes T cells are the key to fighting solid tumors in cancer patients.
The immune system has a big job: every day, it helps to protect us from harmful bacteria and viruses. One component of the immune system, T cells, usually protect us from short-lived illnesses, like viral and bacterial infections. But for some reason, they lose their fighting power when it comes to prolonged diseases like cancer. Versiti Blood Research Institute Investigator Weiguo Cui, MD, PhD, is studying T cells to better understand why they experience something called T cell exhaustion, and why that causes them to lose their ability to fight cancer. If investigators can understand why T cell exhaustion occurs, they may be able to figure out a way to restore or re-energize these calls, causing them to regain function and fight tumors.
“It’s like running a marathon compared with a 100-meter sprint,” Dr. Cui says. “When you get the flu, you’re running a sprint; you have a highly energized immune system. But fighting a tumor is like running a marathon; it’s a long-lasting process that eventually leads to T cell exhaustion.”
A common approach to regain T cell function is called adoptive cell transfer (ACT), which is often seen in transfusion medicine and involves replacing what’s missing. If a patient has dysfunctional T cells, the idea would be to give them functional ones. But T cells are tricky and require strict matching criteria, which is why it’s best to use a patient’s own T cells. The challenge is, patients with cancer have dysfunctional T cells.
Dr. Cui and investigators at Versiti Blood Research Institute recently developed a method that can convert dysfunctional, tumor-fighting T cells into functional, bacteria-fighting T cells. Each T cell has a unique T cell receptor (TCR) that recognizes a specific antigen—it could be a virus like the flu or a tumor like cancer. By isolating T cells with specific receptors from a patient’s tumor, researchers can grow these cells in a lab.
However, these cells still aren’t functional, and if re-introduced to the body, they will travel back to the tumor site. Dr. Cui and his team are working to develop genetically encoded vectors (or DNA molecules) that will lead T cells to express secondary recognition mechanisms. In other words, a cell that recognizes a cancer antigen would also recognize a bacteria antigen—turning into something called a dual-specific T cell. Essentially, these are two sides of the same coin: one side recognizes a tumor (“heads”), while the other (“tails”) recognizes bacteria.
The ultimate goal is to simultaneously transfuse a cancer patient with dual-specific T cells and a vaccine that matches the “tails” bacteria. Because attacking something like bacteria energizes cells and puts them into “sprint” mode, these two-sided T cells will recognize the bacteria first and attack it. Then, they will migrate to the site of the tumor and attack those cancerous cells, clearing the tumor.
This novel therapy, which is unique to Versiti, is still a couple years away from clinical trials. However, Dr. Cui is confident that he and his team are poised to make a big impact in the fields of immunology, cellular therapy and cancer research. “We’re close; from an investigator’s point of view, the groundwork is laid out well. But we need more people and experts to help us move forward,” he says. “If this can work in solid tumors, it will make a big difference.”
Dr. Cui feels that Versiti Blood Research Institute is in the right position to make this innovative therapy a reality. “The Blood Research Institute has a very fostering environment and cultivates innovation,” he says. “We have a very collegial environment that allows interactions between colleagues, which helps to move this research forward.”
Weiguo Cui, MD, PhD, is an investigator at Versiti Blood Research Institute and an associate professor in the Department of Microbiology and Immunology at the Medical College of Wisconsin.