Human immune cells reprogrammed in the laboratory to attack leukemia helped drive out the blood cancer in adults and children with aggressive forms of the disease, according to studies on the new strategy.
The research, reported today at the American Society of Hematology’s annual meeting in New Orleans, showed that 15 of 32 patients with chronic lymphocytic leukemia experienced a reduction of their cancers and 7 achieved remission. In patients with acute lymphoblastic leukemia, 19 of 22 children experienced complete remission, as did all five adults tested.
The technology has now been licensed to Swiss drugmaker Novartis AG (NOVN) to open international trials, said researcher Carl June, a professor of immunotherapy at the University of Pennsylvania. Multicenter trials will start in the U.S. next year at 8 centers around the country, and international trials should begin in 2014, he said.
“This cell therapy is showing a very promising remission rate in both adult and children with advanced leukemia where there is no therapy that works,” June said in a telephone interview. “It’s an exciting time.”
Scientists, led by June, extracted T-cells from patients, genetically modified them to target leukemia cells and then re-infused them. The T-cells, white blood cells that attack infectious invaders, were also instructed to divide in the presence of the cancer, allowing the modified cells to build an army to destroy the malignancies.
June's research group is training people at a manufacturing plant in Morristown, New Jersey in their technique, to broaden the availability of the treatment. The involvement of Novartis will make the treatment more widely available, according to June.
“Every day I have many, many requests to treat people and I have to run them most away because we don’t have the capacity to treat them all,” June said.
CLL is the most common leukemia in adults, accounting for a third of all cases of leukemia, according to the National Cancer Institute. About 15,680 people will be diagnosed in the U.S. this year, and 4,580 people will die. Standard treatments include bone marrow transplant, radiation, and chemotherapy, depending on the stage of cancer. The median survival of the cancer is 8 to 12 years.
ALL is more common in children, though adults comprise about a third of cases. About 6,070 new malignancies will be diagnosed this year, and 1,430 people in the U.S. will die, according to the American Cancer Society. More deaths occur in adults than in children. The cancer progresses quickly. Typical treatments vary with age, though chemotherapy and bone marrow transplant are common.
Two of the three first patients who received treatment in 2010 for CLL are still in remission, and the designer immune cells, nicknamed “CARs” for chimeric antigen receptor, added by scientists to target the cancer, were still circulating. The duration that the cells have lived suggests the treatment is durable, June said.
Among the CLL patients, about half responded to the therapy. One study being presented showed that the dose didn’t matter much as long as the designer immune cells could get a foothold in the body.
In the pediatric patients with ALL, 86 percent experienced remission. The first patient to receive treatment, a girl named Emily, is now 8. She’s been in remission 20 months. Five patients relapsed, including one patient whose cancer didn’t express the protein the cells targeted.
“It’s completely surprising because that disease kills you in weeks,” June said. “We thought that the response rate would be higher in CLL which takes years to kill you but it turns out it’s contrary to what we expected.”
In the 5 adult ALL patients, the longest-treated patient is still in remission after 6 months. One patient underwent a bone marrow transplant and remains in remission; one relapsed after 3 months, with a disease that tested negative for the protein target.
The results in ALL are particularly encouraging, because it’s a fast-progressing disease and particularly fatal, June said.
It’s also easier to tell who’s had a complete response, since the cancer only appears in blood and bone marrow. In CLL, some cancer cells hide in lymph nodes, he said.
June, a former Navy doctor who switched his research focus to cancer from AIDS after his first wife was diagnosed with ovarian cancer, is also looking into other cancers. Multiple myeloma and solid tumors may also respond to the procedure, he said.
“We’re thrilled to see this grow up and head toward applications for a wide body of people,” said Lee Greenberger, chief scientific officer of the Leukemia and Lymphoma Society, which has given $15 million toward the research since 1998.
All of the patients who were treated experienced severe flu-like symptoms, including fevers, chills, nausea and diarrhea. The researchers have managed this by tamping down inflammatory proteins using Roche Holding AG’s Actemra.
The American Hematology Society is the world’s largest professional association concerned with causes and treatment of blood disorders, which include diseases affecting blood, bone marrow, immune, hemostatic and vascular symptoms. The Washington-based group has more than 14,000 members.
Also at today’s meeting, researchers from Dana-Farber/Boston Children’s Cancer and Blood Disorders Center in Boston reported that 8 of 9 children with the rare immune disorder sometimes called bubble-boy disease survived with functioning immune systems after gene therapy treatment.
The rare illness, affecting about 40 to 100 babies each year, leaves them unable to fight germs, making any infection potentially deadly. Researchers used a new approach to gene therapy to repair their immune systems designed to prevent a complication that leads to leukemia.
One of the children died from an overwhelming infection, which was diagnosed as the boy entered the trial.
Of the surviving 8, 7 were producing T-cells. The eighth had a cord blood stem cell transplant. Their survival times vary from 9 to 36 months following their treatment, according to the data.
In gene therapy, scientists replace non-functioning genes with normal ones using a carrier molecule such as a virus; repair abnormal DNA; or alter how the DNA works. Use of the therapy has been controversial, and not always successful. A similar trial a decade ago in Europe led to leukemia in about a third of the patients. Today, the researchers used a different carrier to sneak the new genes into cells.
The bubble boy disorder, formally known as severe combined immunodeficiency, gained national prominence in the late 1970s after reports surfaced about how David Vetter was living in a special bubble-like structure in Texas. Vetter died in 1984, after a bone marrow transplant from his sister failed.
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