Engineered Immune Cells Fight Cancer
December 9, 2013

Engineered Immune Cells Make Big Advance Against Leukemia

Brett Smith for - Your Universe Online

Researchers from the University of Pennsylvania and the Children’s Hospital of Philadelphia have been able to reprogram the body’s immune system to fight leukemia, with 89 percent of children and adults in a series of clinical trials showing no evidence of cancer after receiving a personalized cell therapy.

The findings from the first 59 patients to receive this cutting-edge therapy, known as CTL019, were presented during the American Society of Hematology Annual Meeting and Exposition in New Orleans, held from Dec. 7-10.

"Our results serve as another important milestone in demonstrating the potential of this cell therapy for patients who have no other therapeutic options," said study author Stephan A. Grupp, a professor of pediatrics at the University of Pennsylvania. "We are also very excited that this approach has worked and been safe in patients who have relapsed after a bone marrow transplant."

Two of the first three patients in the study who had chronic lymphocytic leukemia (CLL) remain in remission, the study researchers said. Additionally, tests have shown the reprogrammed cells are still circulating in their bodies and are ready to combat any tumor cells that may show up in the future. The 89 percent success rate was for patients with acute lymphoblastic leukemia (ALL).

"Although most adults with ALL respond to drug treatment, as many as half of them eventually relapse, putting the overall cure rate for the disease only around 40 percent," said study author Dr. David L. Porter, director of blood and marrow transplantation in Penn’s cancer treatment center. "Once a patient relapses, treatments are often ineffective. Many of these patients are not even eligible for bone marrow transplants, so this approach stands to give them an option where they would otherwise have had none."

Of the 32 adult patients with CLL, fifteen responded to the immunotherapy, with seven showing a complete remission of their disease. Of the 22 pediatric patients with ALL, 19 showed a complete remission. The first pediatric patient treated with the protocol was still in remission 20 months later.

The novel technique involved removing patients’ T cells, then reprogramming with a gene transfer technique. The re-engineered T cells are then programmed to target tumor cells by using an antibody-like protein which binds to the surface of the cancerous B cells associated with both CLL and ALL.

After the cells are placed back in the body, they multiply and attack cancer cells. The cells have also been engineered to rapidly proliferate – with tests showing a single cell can grow to more than 10,000 new cells.

"The results from the ALL and CLL trials also demonstrate that these engineered hunter cells greatly expand in patients, producing very high complete response rates, and then persist in patients, potentially allowing for long-term disease control,” Grupp said.

“We are tremendously excited about these results. About half of our CLL patients responded to this therapy, with most of them having several pounds of tumors eradicated by the genetically modified T cells," Porter said.

"We’ve now seen remissions lasting for more than three years, and there are clues that the T cells continue to kill leukemia cells in the body for months after treatment: Even in patients who had only a partial response, we often found that all cancer cells disappeared from their blood and bone marrow, and their lymph nodes continued to shrink over time. In some cases, we have seen partial responses convert to complete remissions over several months.”