CAR T-cell immunotherapy uses our own immune cells to fight cancer. It might eventually do even more.
Nearly 200,000 people will be diagnosed with a form of blood cancer this year. Most of us still think of chemotherapy and radiation when we hear the word, but CAR T-cell therapy is rapidly changing the game of cancer treatments. The treatment uses T-cells — a part of our immune system that normally targets viruses and other diseases.
“We take a batch of T-cells from somebody using a procedure very similar to what’s used for blood donation,” explains pathologist Michael C. Milone, M.D., Ph.D., FASCP, a pioneer in the field. “We then engineer them to express a chimeric antigen receptor (CAR) — a way of synthetically redirecting the T-cell towards a target.”
Search and destroy
Once in the body, these engineered T-cells replicate very, very quickly and go on a “search and destroy” mission looking for the specific target cancer cells. “It’s pretty new,” says Laurie Adami, who was diagnosed with follicular non-Hodgkin lymphoma in 2006. “I heard about it in 2012, when I was on my fifth line of therapy. Nothing had gotten me into remission. At best, I had stable disease.”
Unfortunately for Adami, in 2012 the therapy hadn’t gone through clinical trials for her specific disease. She had to wait six years to get into a clinical trial. Because the therapy was so new and untested, Adami experienced intense side effects. Today, it’s a different story.
“What’s happened in the last five years is we understand the safety profile,” explains Lee Greenberger, Ph.D., chief scientific officer of the Leukemia & Lymphoma Society (LLS), which has been funding CAR T-cell research since the 1990s. “There can be significant safety issues in some patients, but they’re controllable. They don’t persist.”
A month after her treatment, Adami was shocked when her scans showed that her cancer was completely gone. She initially thought she was being deceived. “Now I’m four years out and I’m still clean,” she says. “I believe it.”
An exciting future
These successes are driving further research. “The initial observations have really driven an explosion of research interest,” notes Milone. “People are looking at ways to create really smart T-cells, directing them to where they want to go through very tight regulation.”
“The efficacy is quite remarkable — it works,” stresses Greenberger. “Immunological approaches to control tumors are going to be a very, very important tool in the future.”
There are challenges to overcome, too. Currently, CAR T-cell therapies are primarily what’s known as an “autologous” therapy, meaning the engineered T-cells are created from the patient’s own cells, which are often weakened. “They won’t work very well,” explains Dr. Greenberger, “because they’re just not capable of super-activating like a healthy T-cell. So where are you going to get the T-cells? Well, it turns out, you can get them from donors.”
In what’s known as allogeneic T-cell therapy, the cells can be taken from healthy donors, engineered, and then stored so the therapy is available almost immediately. Greenberger also speculates there may come a time when genetically engineered material could be injected directly, engineering and activating T-cells without needing to harvest them at all.
Dr. Milone sees the future impact of CAR T-cell advances more widely, noting that a single treatment could have a huge impact on poorer areas that struggle to work with “resource intense” cancer treatments, and that the therapy could be applied to different diseases. “The potential applications of CAR T-cell approaches are quite wide ranging,” he says. For Adami, her CAR T-cell experience wasn’t solely about survival. “All of us in those trials were really guinea pigs,” she says, “but they learned a lot. So, I have so much gratitude.”
