In 1996, Doug Olson learned he had chronic lymphocytic leukemia (CLL), a type of cancer that starts in white blood cells. Because this cancer often grows slowly, doctors decided to wait and see what happens.
But years later, when Olson's cancer began to grow, he underwent several rounds of chemotherapy. Then, in 2009, a change occurred in his tumor. Chemotherapy was no longer helpful. Olson's doctor, Dr. David Porter, recommended a bone marrow transplant. However, none of the Olson brothers were a good match.
„The news just seemed to get worse and worse,“ Olson says.
So Olson's doctor suggested a clinical trial of a new type of cancer treatment. Specifically, it was a type of immunotherapy called CAR T-cell therapy. The goal: Reengineer Olson's immune cells in the lab and turn them into weapons to hunt down cancer cells.
CAR T-cell therapy may be effective even when other treatments have not been effective. And unlike chemotherapy and radiation therapy, which kill not only cancer cells but also healthy cells, immunotherapy targets tumors more precisely.
CAR T cell therapy (CAR T) is one type of immunotherapy. Each works in a different way.
Doctors may turn to CAR T when T cells, which normally patrol the bloodstream to find bacteria and other invaders, cannot recognize cancer as a foreign cell. This happens when T cells lack certain proteins that they can bind to to attack tumors.
It's as if „cancer cells have Velcro on them, but the patient's T cells don't have a corresponding Velcro to attach them to,“ says the director of New York University's Cell Therapy and Transplantation Program. Mr. Porter says. Pennsylvania.
With CAR T-cell therapy, your doctor first removes T-cells from your body. Next, he adds a gene to the surface of the T cell that causes it to produce a special protein called a CAR (chimeric antigen receptor) that attaches to cancer cells. After CAR T cells are grown in the lab, doctors put them back into the body.
The reconstituted T cells „have been taught to recognize and kill tumor cells,“ says Renier Brentjens, MD, professor of medicine and director of cell therapy services at Memorial Sloan Kettering Cancer Center.
Not only that, but T cells „can multiply 1,000 to 10,000 times in the body, and each one of those cells can go on to kill more cancer cells,“ Porter says.
Olson received three doses of CAR T cells. After a few weeks, almost 20% of his white blood cells were in his CAR T. When he returned to Porter for tests, „I was told he couldn't find a single cancer cell in my body,“ Olson recalled.
The FDA approved the first CAR T cell therapy in 2017. To date, the FDA has approved two CAR T cell therapies for cancer.
Axicabtagene ciloleucel (Yescarta). It is approved for adults with B-cell lymphoma who have not responded to other treatments or who have relapsed after treatment.
Tissagen le Crucel (Kymriah). It has the same approval as axicabtagene ciloleucel, but can also be used to treat children and young adults with acute lymphoblastic leukemia.
In the study, 9 out of 10 patients with acute lymphoblastic leukemia whose cancer did not respond to other treatments or whose cancer returned went into complete remission with CAR T cell therapy. Remission means that tests do not find cancer.
Complete remission rates for chronic lymphocytic leukemia and non-Hodgkin's lymphoma are lower, ranging from 35% to 70%. Of that number, about one-third remain in long-term remission. „For those people, it definitely lives up to its promise,“ Porter said.
But the problem is, remission isn't necessarily permanent, Brentjens says. In many cases, doctors do not know why the cancer has returned. CAR T cells may not survive long in the body. Or it could eventually be overtaken by a group of T cells that don't have the protein that can hunt down the cancer.
Hair loss, which is common after chemotherapy, does not occur. Instead, CAR T-cell therapy can cause a short-lived but severe reaction called cytokine release syndrome (CRS).
„It's like getting a bad flu,“ says Dr. Terry Fry, a cancer researcher and professor at Children's Hospital Colorado.
Cytokines are proteins released by immune cells when they attack infections. Symptoms include high fever, nausea, chills, headache, rash, and difficulty breathing. CRS can be fatal, but it is treatable in the hospital.
CAR T-cell therapy can also affect the brain, causing confusion, speech problems, and even seizures. Frey said these symptoms usually occur within a few weeks after receiving the infusion and resolve in about a month.
It has been less than 10 years since the first person received CAR T cell therapy. So doctors still don't know anything about the long-term risks.
CAR T cell therapy is effective against blood cancers. But so far, it has not been possible to treat solid tumors such as breast and lung cancer.
Leukemia and lymphoma cells are easier to track because the target protein is on their surface and not present on healthy cells.
Dr. Fry says that „solid tumors are more difficult to crack“ because it is difficult to distinguish between target proteins on cancerous tumors and target proteins on healthy tissue.
Brentjens is one of several researchers looking for ways around this and other hurdles.
“I'm an optimist, so I think within the next five to 10 years we might develop CAR T cells that could potentially target some solid tumors,” he says. . ”
Although there is still work to be done, CAR T-cell therapy has been a life-saving treatment for many who have received it. „A significant proportion of patients treated with these CAR T cells will be long-term survivors, and the patients we are treating are those with little chance of survival,“ Brentjens said. To tell.