Gene therapy has been used to transform patients’ blood cells into soldiers that seek and destroy cancer. A small group of leukemia patients were given a one-time, experimental therapy several years ago and today, some remain cancer-free today. As a follow-up, at least six research groups have treated more than 120 patients with many types of blood and bone marrow cancers, with stunning results.
“It’s really exciting,” says Janis Abkowitz, blood diseases chief at the Univ. of Washington in Seattle and president of the American Society of Hematology. “You can take a cell that belongs to a patient and engineer it to be an attack cell.”
In one study, all five adults and 19 of 22 children with acute lymphocytic leukemia (ALL) showed complete remission of their cancer (i.e. no cancer could be found after treatment), although a few patients have relapsed since then.
These were gravely ill patients who were out of options. Some of them had tried multiple bone marrow transplants and up to 10 types of chemotherapy or other treatments. In the case of eight-year-old Emily Whitehead of Philipsburg, Pa., her cancer was so advanced that her doctors said Emily’s major organs would fail within days. Ms. Whitehead was the first child given the gene therapy and nearly two years later, shows no sign of cancer.
Physicians think that this has the potential to become the first gene therapy approved in the U.S. and the first for cancer worldwide. Only one gene therapy is approved in Europe, for a rare metabolic disease.
This gene therapy involves filtering patients’ blood to remove millions of T-cells, a type of white blood cell. These T-cells are then genetically engineered in the laboratory with a gene that targets cancer. These cells were subsequently returned to the patient in infusions, given over three days.
“What we are giving essentially is a living drug” – permanently altered cells that multiply in the body into an army to fight the cancer, says David Porter, a Univ. of Pennsylvania scientist who led one study.
Several drug and biotech companies are working hard to develop these therapies. The University of Pennsylvania has patented its method and licensed it to the Switzerland-based company Novartis AG. Novartis AG is building a research center on the Penn campus in Philadelphia and plans a clinical trial next year that could lead to federal approval of the treatment as soon as 2016. Hervé Hoppenot, president of Novartis Oncology, the division leading the work, said that “there is a sense of making history… a sense of doing something very unique.” Lee Greenberger, chief scientific officer of the Leukemia and Lymphoma Society, agrees: “From our vantage point, this looks like a major advance. We are seeing powerful responses… and time will tell how enduring these remissions turn out to be.”
This group has given $15 million to various researchers who are testing this strategy. Since there are nearly 49,000 new cases of leukemia, 70,000 cases of non-Hodgkin lymphoma and 22,000 cases of myeloma expected to be diagnosed in the U.S. in 2013, there are no shortage of potential subjects.
Many patients are successfully treated with chemotherapy or bone marrow or stem cell transplants, but transplants are risky and donors can’t always be found. Thus, gene therapy has been used as a fallback strategy for patients who were in danger of dying once all the other treatments failed.
The gene therapy must be made individually for each patient, since laboratory costs now are about $25,000, without a profit margin. That’s still less than many drugs to treat these diseases and far less than a transplant. The treatment can cause severe flu-like symptoms and other side effects, but these have been reversible and temporary, according to the physicians who administer the gene therapy treatment and observe the patients afterwards.
Penn doctors have treated 59 patients so far, which is the most of any center so far. Of the first 14 patients with B-cell chronic lymphocytic leukemia (CLL), four showed complete remissions, four showed partial remission, and the remaining patients did not respond to the treatment. However, some of the patients who showed partial remission continued to see their cancer shrink a year after treatment. “That’s very unique to this kind of therapy” and gives hope the treatment may still purge the cancer, says Porter.
Another 18 CLL patients were treated and half have responded so far. University of Pennsylvania doctors also treated 27 ALL patients. All five adults and 19 of the 22 children had complete remissions, which is an “extraordinarily high” success rate, according to Stephan Grupp at the Children’s Hospital of Philadelphia (CHOP). Six patients have, since then, suffered relapse of their cancer. The attending physicians are considering administering a second gene therapy treatment.
At the National Cancer Institute, James Kochenderfer and others have treated 11 patients with lymphoma and four with CLL, starting roughly two years ago. Six showed complete remission, six patients had partial remission, and one has stable disease but it is too soon to tell for the rest.
Ten other patients were given gene therapy to try to kill the leukemia or lymphoma cells that remained after bone marrow transplants. These patients received infusions of gene-treated blood cells from their transplant donors instead of using their own blood cells. One had a complete remission and three others had significant reduction of their disease.
“They’ve had every treatment known to man. To get any responses is really encouraging,” Kochenderfer says. The cancer institute is working with a Los Angeles biotech firm, Kite Pharma Inc., on its gene therapy approach.
Patients are encouraged that relatively few have relapsed.
“We’re still nervous every day because they can’t tell us what’s going to happen tomorrow,” says Tom Whitehead, eight-year-old Emily’s father.
Doug Olson, 67, a scientist for a medical device maker, shows no sign of cancer since his gene therapy in September 2010 for CLL he has had since 1996. “Within one month he was in complete remission. That was just completely unexpected,” says Porter, his doctor at Penn. Olson ran his first half-marathon in January and no longer worries about how long his remission will last. “I decided I’m cured. I’m not going to let that hang over my head anymore,” he says.
Beyond the Dish 