Translational Research on Recurrent Metastatic Neuroblastoma Occurring at Children’s Hospital Los Angeles

Proof-of-concept study using dinutuximab and activated natural killer
cells leads to a clinical trial

LOS ANGELES–(BUSINESS WIRE)–Neuroblastoma, a disease of immature nerve cells, is the most common
solid tumor cancer occurring in children. About 700 new cases are
diagnosed in the U.S. each year with approximately half of these
children developing high-risk disease, which has a 40 to 50 percent
chance of survival.

In 2015, the Food and Drug Administration approved a monoclonal antibody
called dinutuximab
for treatment of high-risk neuroblastoma. The approval followed a
ground-breaking study, led by the Children’s Oncology Group and
published in the New England Journal of Medicine. This pivotal trial
halted enrollment earlier than planned because the therapy showed
significant improvement in survival over the standard treatment.

Although dinutuximab is a game-changing treatment in the battle against
neuroblastoma, the fact remains – children are still dying from this
disease,” said Eugene
S. Kim, MD
, surgical oncologist at Children’s Hospital Los Angeles.

A team, led by Kim, designed basic research studies that would go beyond
using tumor-shrinkage as a marker of efficacy and instead focus on
recurrent disease and overall survival. The team’s approach was to
create a model system that more faithfully replicates the patient

Patients with neuroblastoma undergo surgery to remove their tumor and
then have subsequent therapy. Children with resistant or recurrent
disease initially improve but then their tumor returns, and they succumb
to the disease. For this study, the investigators mimicked the treatment
protocol and developed a new, clinically relevant model for studying
metastatic disease.

In this model, metastatic tumors were surgically removed and, once the
disease recurred, dinutuximab was used, along with activated human
natural killer (NK) cells, which are a ”supercharged” subset of white
blood cells, to actively target and kill cancer cells.

Not only did we see tumor shrinkage, we saw a reduction in metastatic
disease and a significant increase in survival,” said Kim, an associate
professor of Surgery at the Keck School of Medicine of USC. Results of
the study were recently published in Clinical
Cancer Research

The findings were sufficiently compelling that they provided
proof-of-concept for a clinical trial at CHLA, which will be enrolling
patients in the near future. The study, which will incorporate the use
of activated natural killer cells with dinutuximab therapy in patients,
is led by Araz
Marachelian, MD
, director of the neuroblastoma program at CHLA and
medical director of the New
Approaches to Neuroblastoma Therapy (NANT) Consortium

First author, Wesley E. Barry, of CHLA, received the prestigious Young
Investigator Award at the 2018 Advances in Neuroblastoma Research
Conference, for his work on this study. Additional contributors include
Jeremy R. Jackson, Grace E. Asuelime, Hong-Wei Wu, Jianping Sun, Zesheng
Wan, Jemily Malvar, Michael A. Sheard, Larry Wang, Robert C. Seeger, all
of CHLA.

The study was supported by Children’s Hospital Los Angeles Institutional
Start-up Funding and, in part, by grant 1 P01 CA217959 from the National
Cancer Institute.

About Children’s Hospital Los Angeles

Founded in 1901, Children’s Hospital Los Angeles is ranked the top
children’s hospital in California and sixth in the nation for clinical
excellence with its selection to the prestigious U.S. News & World
Report Honor Roll of children’s hospitals. Clinical care is led by
physicians who are faculty members of the Keck School of Medicine of USC
through an affiliation dating from 1932. The hospital also leads the
largest pediatric residency training program at a freestanding
children’s hospital of its kind in the western United States. The Saban
Research Institute of Children’s Hospital Los Angeles encompasses basic,
translational and clinical research conducted at CHLA. To learn more,
follow us on Facebook, Instagram, LinkedIn and Twitter, and visit our
blog for families (CHLA.org/blog) and our research blog


Children’s Hospital Los Angeles
Ellin Kavanagh, 323-361-8505


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