Advanced Cell Therapy Eliminates Aggressive Leukemia in Two Children

The investigators, Stephen A. Grupp, MD, PhD and Carl H. June, MD, engineered T cells — the workhorses of the immune system, which recognized and attack invading disease cells — to selectively kill another type of immune cell called B cells, which had become cancerous.

According to new research from The Children’s Hospital of Philadelphia and the University of Pennsylvania, two children with an aggressive form of childhood leukemia achieved a complete response after being treated with an innovative cell therapy. In the study, both patients’ immune systems were reprogrammed to rapidly multiply and destroy leukemia cells.

The study was published online Monday in The New England Journal of Medicine, and is set to appear in the April 18 print issue.

Both patients were treated for acute lymphoblastic leukemia (ALL), an aggressive childhood leukemia. The most common form of leukemia found in children, ALL is largely curable, with a roughly 85 percent cure rate. However, the remaining 15 percent of ALL cases resist standard therapy.

The research team used a relatively new approach in cancer treatment: immunotherapy, in which the immune system is manipulated to increase its cancer-fighting capabilities. The investigators engineered T cells — the workhorses of the immune system, which recognized and attack invading disease cells — to selectively kill another type of immune cell called B cells, which had become cancerous.

Dr. Stephen A. Grupp and Emily, recipient of cell therapy.

One of the patients treated, 7-year-old Emily Whitehead, was the subject of a media frenzy last year when the experimental therapy led to her dramatic recovery after she relapsed following conventional treatment. 11 months after receiving bioengineered T cells, Emily remains healthy and cancer-free.

The other patient, a 10-year-old girl who also had a complete response to the same treatment, suffered a relapse two months later when other leukemia cells appeared that did not harbor the specific cell receptor targeted by the therapy.

“This study describes how these cells have a potent anticancer effect in children,” said the study’s co-first author Stephan A. Grupp, MD, PhD, the Center for Childhood Cancer Research’s director of Translational Research. “However, we also learned that in some patients with ALL, we will need to further modify the treatment to target other molecules on the surface of leukemia cells.”

The current study builds on Dr. Grupp’s ongoing collaboration with Penn Medicine scientists — led by the study’s senior author, Carl H. June, MD — who originally developed the modified T cells as a treatment for B-cell leukemias in adults. And though early results have been promising, the research team continues to refine their approach to using this new technology and to explore why some patients may not respond to the therapy or may experience a recurrence of their disease.

“The emergence of tumor cells that no longer contain the target protein suggests that in particular patients with high-risk ALL, we may need to broaden the treatment to include additional T cells that may go after additional targets,” said. Dr. Grupp. “However, the initial results with this immune-based approach are encouraging, and may later even be developed into treatments for other types of cancer.”

For more information about this exciting, groundbreaking study, see the full press release.