New treatment for medulloblastoma in children

The TB-403 antibody recognizes placental growth factor (PlGF), which is overexpressed in certain types of malignancies.

A recent Phase I clinical trial conducted by researchers at Atrium Health Levine Children’s Hospital and Massachusetts General Hospital (MGH) in the United States has generated promising results in a new antibody treatment for him meduloblastomathe kind of most common cancerous brain tumor in children.

The novel blocking antibody therapy they target a protein essential to the ability of medulloblastoma cells to multiply and spread, researchers report in Clinical Cancer Research, a journal of the American Association for Cancer Research.

The antibodynamed TB-403recognizes placental growth factor (PlGF), overexpressed in some types of malignancies. The MGH research team previously demonstrated that PlGF and its receptor neuropilin 1 (NRP1) are often overexpressed in human medulloblastomas and are required for their growth and progression in experimental mouse models (Cell 2013). This work also showed that the PlGF/NRP1 pathway blockade in medulloblastoma models, it caused tumor regression, decreased spread to the spinal cord, and prolonged survival.

“Beyond new biological knowledge, the the experimental results were particularly exciting because blocking PlGF, unlike other cancer-related pathways, was safe in humans and therefore a particularly promising strategy in the pediatric population,” explains the lead author. Rakesh K.Jain, Director of the EL Steele Laboratories for Tumor Biology at the MGH and Professor of Radiation Oncology at Harvard Medical School. To this he adds that they are “delighted to see the initial translation of these concepts into a clinical trial“.

The study included the participation of 15 children.

In an open-label, multicenter, investigator-led, dose-escalation study 15 children with medulloblastoma participated relapsers or refractories who have not responded to standard treatments. Patients received increase in antibody doses against human PlGF TB-403 (20 mg/kg, 50 mg/kg, 100 mg/kg, and 175 mg/kg), and all patients received two doses of TB-403 during the first treatment cycle. The maximum tolerated dose, defined in clinical trials as the highest dose of a drug that does not cause unacceptable toxicity, was not reached.

Moreover, although there was no partial tumor responses (significant reductions in tumor size) In this treatment-refractory population, seven of the 11 patients experienced disease stabilization – arrest of progression – which persisted for more than 100 days in four of them. The researchers concluded that the treatment with TB403 it was well tolerated and induced stabilization of the disease in certain medulloblastomas in a context where effective treatments were not available.

“These results indicate that the treatment with TB-403 should be tested in larger studies of children with advanced and possibly anterior medulloblastoma, in combination with standard therapies,” said lead and corresponding author Giselle L. Saulnier Sholler, MD, program director on Solid and Rare Tumors at the Isabella Santos Foundation and Chair of the Levine Children’s Hospital Beat Childhood Cancer Research Consortium.

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