A Combined Strategy to Treat Neuroblastoma

With his first National Institute of Health R01 award, Dr. Christian Capitini will lead preclinical research that combines immunotherapy treatment strategies for neuroblastoma with innovative real-time imaging.
With his first National Institute of
Health R01 award, Dr. Christian Capitini
will lead preclinical research that
combines immunotherapy treatment
strategies for neuroblastoma with
innovative real-time imaging.

A new preclinical research project led by Department of Pediatrics Assistant Professor Christian Capitini, MD, aims to strengthen the pipeline of immunotherapy treatment approaches for neuroblastoma, the third most common type of childhood cancer.

The five-year, $1.75 miilion project, “Combining hu14.18-IL2 and NK cell infusions to treat neuroblastoma,” is funded by the National Institutes of Health’s (NIH) National Cancer Institute, and is Dr. Capitini’s first NIH R01 award as a principal investigator. (Read more about Dr. Capitini’s lab.)

Sean Fain, PhD, a professor in the Department of Medical Physics and director of its Image Analysis Core Facility, MRI and CT Imaging, is a co-investigator.

Two Immunotherapy Approaches

Using a mouse model, Dr. Capitini’s team will combine two immunotherapeutic approaches for neuroblastoma treatment.

First, they’ll transplant donor bone marrow cells into tumor-bearing mice and administer an antibody (the immunocytokine hu14.18-IL2) to strengthen the new immune system’s capacity to attack the tumor. Then, they’ll infuse immunologically activated natural-killer (NK) cells from the donor to further target and attack the tumor.

The aim of the combined approaches are to redirect the new immune system to eliminate the neuroblastoma tumor, while reducing the risk of graft-versus-host disease (GVHD), a life-threatening immune reaction commonly seen after bone marrow transplant.

Real-Time Imaging

In addition, the team will use a new type of real-time imaging to track the NK cells’ progression through the body. They’ll label the NK cells with fluorine-19, a non-radioactive isotope of fluorine, and then detect them with a magnetic resonance imaging (MRI) coil developed with Dr. Capitini’s colleagues in the Department of Medical Physics.

“Right now, we have to draw blood or do a bone marrow biopsy to detect the injected NK cells,” explains Dr. Capitini. “With this technique, I can do an MRI within hours of infusion and get high-resolution images to see if the NK cells find the tumor.”

“Most centers use positron emission tomography (PET) scans for real-time imaging, but the radioactive agents used for them decay within hours or days,” he continues. “But because fluorine-19 isn’t radioactive, we can track NK cells for as long as they’re alive, even months later.”

Building on a Platform of Research

Dr. Capitini’s strategy dovetails with similar immunotherapeutic treatment approaches currently in clinical trials led by two Department of Pediatrics colleagues, Mario Otto, MD, PhD, and Kenneth DeSantes, MD.

Dr. Otto leads a Phase I trial in which clinicians first deplete the T-cells known to cause GVHD from donor stem cells before transplanting them into the patient. The University of Wisconsin is the only center that uses this approach for solid tumors, such as neuroblastoma, as well as for hematologic cancers.

Dr. Desantes leads a new Phase I trial that combines NK cells from a half-matched donor, typically a parent, with an antibody to better target a neuroblastoma tumor prior to transplant.

“We’re combining the approaches used in those trials to see if they’re safe and effective in a preclinical model,” Dr. Capitini says. “We hope our study will not only serve as a pipeline for future trials, but also show that our approach to image-guided therapy, if successful, could be used for other applications.”