clock menu more-arrow no yes

Filed under:

Blood cells, honed in the lab to kill cancer, lead to four-year remissions

Three of 14 leukemia patients are in complete remission

Penn Medicine

Four years after being treated with modified versions of their own blood cells, three of 14 cancer patients are in complete remission. And they haven’t had any additional treatment in that time.

The report published in Science Translational Medicine is a follow-up to a study published in 2011, which described the treatment in people with chronic lymphocytic leukemia for the first time. The results of today’s study show that four people experienced a partial remission; another four had undetectable levels of the cancer. (One of those patients died while in remission, from complications of removing a skin cancer lesion on his leg). Among the people who didn’t respond to the therapy, two died; the other four are still alive and receiving other treatments.

Chronic lymphocytic leukemia is "essentially incurable today."

Chronic lymphocytic leukemia is a type of cancer of the blood and bone marrow that's "essentially incurable today," says Michel Sadelain, an immunologist at Memorial Sloan-Kettering who didn't work on the study. This year, an estimated 14,620 people will be diagnosed with CLL, and 4,650 people will die of the disease. Some patients can become disease-free thanks to stem cell transplant treatments, but these treatments are complicated and often don’t work, Sadelain says. So for the most part, common treatments like chemotherapy only serve to prolong a patient's life. That's why something like this blood cell-based treatment is such a big deal. The overall response rate in the study was 57 percent — a huge achievement for a form of cancer that used to kill most people in a median time of 8 to 12 years.

"In the summer of 2010, I was 65 and I didn't think I'd see Christmas," says Bill Ludwig, now 70. He was first diagnosed with leukemia in 2000; he underwent multiple rounds of chemotherapy following his diagnosis, but the cancer kept coming back. So, in August of 2010, Ludwig was given a dose of his own modified blood cells. Now, he's keeping busy by traveling in an RV with his wife. "We started to take little trips here and there in 2011, after I had no cancer for a year," he says. "And we've been doing that ever since."

"In the summer of 2010, I was 65 and I didn't think I'd see Christmas."

The therapy that Ludwig received works like this: first, doctors take a patient’s blood and spin out the T cells, white blood cells that hunt down invaders as part of the immune system. Then, in the lab, the T cells undergo gene therapy that trains them to hunt a protein expressed only on the surface of B cells, the type of blood cell that’s affected in leukemia. Then, the retrained cells are infused back into the patient’s bloodstream, where they hunt all B cells — even if they aren’t cancerous. So people who respond to therapy have to live without a part of their immune systems; not ideal, but better than death.

"This is a whole new approach to treating cancer," says David Porter, a leukemia researcher at the University of Pennsylvania and a co-author of the study. By modifying T cells, scientists have found a way to harness the human immune system so it can hunt down and kill cancerous cells. And what's even more exciting is that scientists have been able to detect these T cells for years after they were first administered. "This is a living drug," Porter says — the T cells "grow and live in the body." And now, scientists are learning that their activity is long-lasting.

"This is a living drug."

"It's good news for patients with CLL, and good news for the field," Sadelain says — but the therapy is still a work in progress.

Besides the loss of B cells, the therapy triggers one pretty important side effect, called "cytokine release syndrome." All of the patients who responded to the treatment experienced this condition, which causes the immune system to go into hyperdrive. Patients had fevers, nausea, low blood pressure, and even problems breathing after receiving the therapy. A drug can be used to treat these symptoms, but it's unclear when it should be administered, Porter says; researchers worry that these side effects might be necessary to make the treatment work; if that's the case, administering the drug too early could put the T cell therapy's effectiveness in jeopardy.

Ludwig was hit hard by the syndrome. "I was in a sad condition, but then slowly my body calmed down," he says. As far as he's concerned, it was worth it.

The T cell therapy has been used on another form of leukemia, called "acute lymphocytic leukemia." It actually worked a lot better on patients with that disease; about 90 percent of people with ALL have responded to the treatment. So, even though the results for the CLL treatment are encouraging, both Porter and Sadelain think they could be a lot better. Researchers working on this therapy want to figure out what’s contributing to the treatment’s effectiveness — or to CLL’s resistance. So far, they have eliminated factors like a patient’s age and the amount of therapy they’ve received in the past.

"CLL seems to still have some mechanisms of resistance, at least in some of the patients," says Sadelain, who has used the treatment on patients with leukemia. "So what exactly is the nature of that resistance? And how can we overcome it?"

Researchers want to know why it works on some people, but not on others

The method has been used on patients with leukemia and patients with Hodgkin's lymphoma. But scientists think it could also be used on many other forms of cancer, notably on ovarian and pancreatic cancer. "If you can identify a unique target on the tumor, this technology can be applied to other cancers," Porter says. And it's that possibility that really has researchers excited.

Today's study "shows that we can now modify the human immune system to effectively and efficiently treat cancer," Porter says — "and that's going to open doors to a whole new world of cancer therapies."