Leukemia Patient Cancer-Free After Novel Treatment With Engineered Immune Cells

Cancer therapy for children has come a long way over the last several decades, and the cure rate for some forms of pediatric cancer is at an all-time high. Although this success rate offers tremendous hope and optimism, there are some children whose disease fails to respond to conventional treatment, leaving doctors to explore novel ways to conquer cancer.

A pediatric oncologist at The Children’s Hospital of Philadelphia achieved a complete response in one of his patients by using an innovative treatment approach that involved reprogramming the child’s own immune cells to attack an aggressive form of childhood leukemia, called acute lymphoblastic leukemia (ALL). Physicians can cure roughly 85 percent of ALL cases but the remaining 15 percent of such cases resist standard therapy.

The prospects for 7-year-old Emily (Emma) Whitehead were grim when her cancer relapsed after she received the conventional treatment for ALL, the most common form of childhood leukemia and the most common childhood cancer. Faced with few viable treatment options, oncologist Stephan A. Grupp, MD, PhD, tried an experimental therapy using bioengineered T cells that were custom-designed to multiply rapidly and destroy leukemia cells.

Emma received the therapy as part of a research clinical trial conducted by investigators at the Perelman School of Medicine at the University of Pennsylvania and CHOP. Three weeks after the treatment, Emma’s doctors found no evidence of cancer.

The research by Dr. Grupp, director of Translational Research for the Center for Childhood Cancer Research at CHOP, builds upon his ongoing collaboration with Penn scientists who originally developed the modified T cells as a treatment for B-cell leukemias. The Penn team, led by Carl H. June, MD, reported on early results of a trial using

this cell therapy in adult chronic lymphocytic leukemia patients in August 2011. Dr. Grupp and his colleagues at Penn then adapted the treatment for use in treatment-resistant ALL cases.

The investigators presented new data on the clinical trial at the American Society of Hematology annual meeting today, reporting that nine of 12 patients with advanced leukemias — including Emma and one other pediatric patient — responded to treatment with CTL019 cells.

The CTL019 therapy, formerly called CART19, represents a new approach in cancer treatment. As the workhorses of the immune system, T cells recognize and attack invading disease cells. However, cancer cells fly under the radar of immune surveillance, evading detection by T cells. CAR T cells (chimeric antigen receptor T cells) are engineered to specifically target B cells, which become cancerous in certain leukemias like ALL and CLL, as well as types of lymphoma, another cancer of the immune cells.

“These engineered T cells have proven to be active in B cell leukemia in adults,” said Dr. Grupp. “We are excited to see that the CTL019 approach may be effective in untreatable cases of pediatric ALL as well. Our hope is that these results will lead to widely available treatments for high-risk B cell leukemia and lymphoma, and perhaps other cancers in the future.”

The pioneering research also underscores the importance of timing when considering experimental therapies for relapsed patients.

“To ensure newly relapsed patients with refractory leukemia meet criteria for options like CTL019, we must begin exploring these innovative approaches earlier than ever before,”added Susan R. Rheingold, M.D., one of the leaders in the Children’s Hospital program for children with relapsed leukemia. “Having the conversation with families earlier provides them more treatment options to offer the best possible outcome.”

In August 2012, Novartis acquired exclusive rights from Penn to CART-19, the therapy that was the subject of this clinical trial and which is now known as CTL019.

For more information on childhood cancer and the services offered at CHOP, visit the Hospital’s Cancer Center.