Medulloblastoma, the most prevalent form of malignant brain tumor in children, requires effective and reliable therapies, especially for kids whose cancer has spread to the spinal cord.

A novel blocking antibody treatment that targets a protein crucial to the ability of medulloblastoma cells to proliferate and spread has produced promising results in a recent phase I clinical trial led by researchers from Atrium Health Levine Children’s Hospital and Massachusetts General Hospital (MGH).

Clinical Cancer Research, an AACR journal, published the findings.

The antibody, TB-403, targets placental growth factor (PlGF), which is overexpressed in several kinds of cancer.

Previously, the MGH research team demonstrated that PlGF and its receptor Neuropilin 1 (NRP1) are frequently overexpressed in human medulloblastomas and are necessary for its development in experimental mouse models (Cell 2013).

In addition, inhibiting the PlGF/NRP1 pathway in medulloblastoma animals promoted tumor regression, decreased spinal cord dissemination, and prolonged survival.

Beyond the new biological understandings, Rakesh K. Jain, senior author of the study, says that “the experimental results were particularly exciting because blocking PlGF, unlike other cancer-related pathways, was safe in humans and thus was a particularly promising strategy in the pediatric population.” 

“We are thrilled to see the initial translation of these concepts into a clinical trial.”

15 kids with relapsed or refractory medulloblastoma who had not responded to traditional therapies were enrolled in the researchers’ phase I, open-label, multicenter dose-escalation study. The anti-human PlGF antibody TB-403 was administered to patients at escalating doses (20 mg/kg, 50 mg/kg, 100 mg/kg, and 175 mg/kg), and all patients got two doses of TB-403 during the first cycle of therapy.

Clinical trials did not achieve the maximum tolerated dose, which is the largest dose of a medicine that does not produce unacceptable toxicity.

However, despite the fact that there were no partial tumor responses (meaningful decreases in tumor size) in this group of patients who had failed treatment, seven of the 11 patients did experience disease stabilization, which is the halting of disease progression, and which lasted for more than 100 days in four of those patients.

The researchers came to the conclusion that TB403 treatment was well tolerated and caused stable illness in some medulloblastomas in a situation when there were no other accessible therapeutic treatments.

According to lead and coauthor author Giselle L. Saulnier Sholler, “These findings indicate that treatment with TB-403 should be tested in larger studies of children with advanced medulloblastoma and perhaps at earlier stages, in combination with standard therapies.”

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