Immunotherapy for Children with High-Risk Neuroblastoma

Paul Sondel, MD, PhD
Research from the laboratory of Professor
Paul Sondel, MD, PhD, has played a key
role in an effective new treatment for
high-risk neuroblastoma.

Research from the laboratory of Professor Paul Sondel, MD, PhD, has played a key role in the development and testing of an effective new treatment for some children with high-risk neuroblastoma.

Neuroblastoma is a cancer of the sympathetic nervous system most commonly found in children under the age of five. Nearly half of neuroblastoma cases are considered “high-risk,” meaning that the disease is likely to spread aggressively—and the child is likely to die—if only standard chemotherapy treatment is given.

Last year, Dr. Sondel and members of the Children’s Oncology Group led a National Institutes of Health-funded Phase III trial to test whether a new form of immunotherapy is more effective than standard therapy for these high-risk patients.

Immunotherapy Extends Survival by 20 Percent

In the trial, investigators randomly assigned 226 children who had finished all neuroblastoma chemotherapy treatments into two treatment groups:

  • The first group received the standard therapy of six cycles of isotretinoin.
  • The second group received the new immunotherapy treatment: six cycles of isotretinoin plus five cycles of the monoclonal antibody ch14.18, in combination with alternating GM-CSF and interleukin-2. (Both GM-CSF and interleukin-2 are white blood cell activators, which enables them to use the ch14.18 antibody to more effectively kill neuroblastoma cells.)

Study results after two years showed that the rate of survival—without relapse or disease progression— was 20 percent greater in the children who received immunotherapy (66% versus 46%).

This immunotherapy treatment has become the standard approach used by the Children’s Oncology Group, which cares for approximately 90% of children with cancer in the US and Canada.

The full study was published in the New England Journal of Medicine on September 30, 2010.

The Laboratory Connection

The immunotherapy treatment used in the trial is based in part on work from Dr. Sondel’s laboratory. For over 60 years, basic science researchers there have been evaluating immunological methods focused on improved cancer treatment. For approximately 30 years, some of this work has incorporated the use of tumor-reactive monoclonal antibodies for destroying cancers, including neuroblastoma.

Over 20 years ago, Dr. Sondel’s team showed that administering interleukin-2 to cancer patients can activate certain white blood cells (“natural killer” cells) to a state where they are able to more potently destroy neuroblastoma cells that had been treated with a tumor-specific monoclonal antibody.

“We are pleased that this immunotherapy regimen has now become the standard of care in the US for children with high-risk neuroblastoma,” Dr. Sondel said.

“We are now investigating the use of personalized medicine to identify individuals with certain genes that might make them most likely to benefit from this treatment,” he added. “In addition, through collaborative genetic engineering, we are testing an exciting next generation of this treatment, in which the interleukin-2 is linked directly to the monoclonal antibody. This genetically engineered agent works far better in mice than the prior combination, and our initial clinical testing has generated promising results.”