In 1996, Doug Olson discovered he had chronic lymphocytic leukemia (CLL), a form of cancer that starts in the white blood cells. This cancer often grows slowly, so his doctor decided to watch it and wait to treat it.
But when Olson’s cancer began to grow a few years later, he underwent several rounds of chemotherapy. Then, in 2009, the tumor changed. Chemo no longer helped. Olson’s doctor, David Porter, MD, recommended a bone marrow transplant. But none of Olson’s siblings were a good fit.
“It seemed like the news was getting worse and worse,” Olson said.
Then Olson’s doctor suggested a clinical trial for a new type of cancer treatment. Specifically, it was a form of immunotherapy called CAR T-cell therapy. The goal: redesign Olson’s immune cells in the laboratory and turn them into weapons to detect cancer cells.
CAR T-cell therapy may work when other treatments have not. And unlike chemotherapy and radiation, which kill both healthy and cancerous cells, immunotherapy targets tumors with more precision.
CAR T cell therapy, or CAR T, is one of the few types of immunotherapy. Everyone works in a different way.
Doctors may turn to CAR T when T cells, which normally patrol the bloodstream to detect germs and other invaders, cannot recognize cancer as a foreign cell. This happens when the T cells lack the specific proteins that can bind to the tumor and attack it.
It’s as if “the cancer cell has a piece of Velcro, but the patient’s T cells don’t have the corresponding piece of Velcro to make it stick,” says Porter, director of the Cell Therapy and Transplant Program at New York University. Pennsylvania.
During CAR T cell therapy, doctors first remove T cells from your body. They then add a gene that causes the T cells on their surfaces to produce special proteins called CARs (chimeric antigen receptors) that can attach to the cancer cells. After the CAR T cells multiply in the laboratory, doctors place them back into your body.
The redesigned T cells “are trained to recognize and kill the tumor cells,” says Renier Brentjens, MD, PhD, professor of medicine and director of the cell therapy service at Memorial Sloan Kettering Cancer Center.
And not only that: the T cells “expand in the body a thousand to ten thousand times. And each of these cells can kill even more cancer cells,” says Porter.
Olson received three doses of CAR T cells. After a few weeks, almost 20% of his white blood cells were CAR T. When he returned to Porter for tests, “he told me they couldn’t find a single cancer cell in my body,” Olson recalls.
The FDA approved the first CAR T-cell therapy in 2017. To date, the agency has approved two CAR T-cell therapies for cancer.
Axicabtagene ciloleucel (Yescarta). This is approved for B-cell lymphoma in adults who have not responded to other treatments or have come back after treatment.
Tisagenlecleucel (Kymriah). This has the same approval as axicabtagene ciloleucel, but can also be used to treat children and young adults with acute lymphocytic leukemia.
Studies show that 9 out of 10 people with acute lymphocytic leukemia whose cancer did not respond to other treatments or whose cancer came back had complete remission with CAR T-cell therapy. Remission means the cancer cannot be found in tests.
Complete remission rates for chronic lymphocytic leukemia and non-Hodgkin’s lymphoma are lower: 35% to 70%. Of that number, about a third have long-term remissions. “For those people, it absolutely delivers on the promise,” Porter says.
But the problem is that remissions are not always permanent, says Brentjens. In many cases, doctors don’t know why the cancer returns. CAR T cells may not remain in the body for long. Or they may eventually be overtaken by a group of T cells that lack the protein that can chase away the cancer.
You will not have the hair loss that usually follows chemotherapy. Instead, CAR T-cell therapy can lead to a short-lived but severe reaction called cytokine release syndrome, or CRS.
“It’s similar to a terrible case of the flu,” says Terry Fry, MD, cancer researcher and professor at Children’s Hospital Colorado.
Cytokines are proteins that immune cells release when they attack an infection. Symptoms include high fever, nausea, chills, headache, rash and difficulty breathing. CRS can be fatal, but is treatable in a hospital.
CAR T-cell therapy can also affect the brain, causing confusion, speech problems and sometimes seizures. Usually, Fry says, these symptoms occur within a few weeks of the infusion and get better in about a month.
It has been less than a decade since the first person received CAR T-cell therapy. Doctors are therefore still not aware of any long-term risks.
CAR T-cell therapy works for blood cancer. But so far it has failed to treat solid tumors such as breast or lung cancer.
Leukemia and lymphoma cells are easier to detect because the targeted protein is on the surface and because they are not on healthy cells.
Fry says that “solid tumors are a harder nut to crack” because it is more difficult to distinguish between targeted proteins located on cancerous tumors and those on healthy tissue.
Brentjens is one of the researchers who is looking for ways to circumvent these and other obstacles.
“I’m an optimist, so I would say that in the next five to 10 years we might have some CAR T cells that could potentially target some solid tumors,” he says. “But this is still a work in progress.”
Although there is still work to be done, CAR T-cell therapy has been a life-saving treatment for many of the people who have undergone it. “A significant proportion of patients treated with these CAR T cells will be long-term survivors. And the patients we treat are those whose survival expectancy was zero,” says Brentjens.