Neuroblastoma cells microscope image
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Research led by Baylor College of Medicine and Texas Children’s Cancer Center shows hopeful results in a first-in-human phase I clinical trial using genetically engineered natural killer T cell (NKT) immunotherapy to treat neuroblastoma.

Neuroblastoma is the most common cancer in infants, arising from immature nerve cells and predominantly affecting the adrenal gland. While low-risk variants of neuroblastoma are relatively easy to treat, high-risk variants often require invasive radiation—or chemotherapy—exposing the young patients to a plethora of serious side effects.

Reporting in Nature Medicine, researchers have now developed a novel neuroblastoma immunotherapy using modified NKT cells that express a GD2-specific chimeric antigen receptor. This receptor allows the immune cells to attack a molecule found on the surface of neuroblastoma cells as well as activate a natural protein called interleukin-15 which supports NKT survival.

The study involved 12 patients with stage four relapsed neuroblastoma that was unresponsive to other therapies. According to the researchers, the therapy was safe for all patients on four dose levels with no reports of dose-limiting toxicities. Twenty-five percent of patients showed response to treatment and an additional fifteen percent also showed evidence of antitumor activity such as a reduction of metastatic tumor burden.

“We are encouraged by the evidence of antitumor activity that has been observed in several patients, particularly since this trial is still in the dose escalation phase,” said Andras Heczey, PhD, associate professor of pediatrics at Baylor College of Medicine and co-author of the study in a press statement.

Previously, the researchers had identified that NKT cells can localize to neuroblastoma sites in the body in pre-clinical models. The scientists also discovered a link between higher antitumor activity and in vivo proliferation of the administered CAR-NKT cells.

“We cannot always predict the extent of NKT cell expansion in vivo after infusion,” said Leonid Metelitsa, PhD, professor of pediatrics at Baylor College of Medicine and co-author of the study. “In this study, we found the CD62L biomarker expressed on the infused NKT cells, which we identified in our preclinical work, is predictive of both higher NKT cell in vivo expansion and antitumor activity in patients.”

Following the promising interim results, the trial has been expanded to include two higher doses of the CAR-NKT cells. Upon completion of phase one, the researchers are planning to conduct a phase two trial to further investigate the antitumor activity of the neuroblastoma therapy.

“This study provides promising initial evidence of antitumor activity of GD2 CAR NKT cells against neuroblastoma. This inspires hope that novel immunotherapeutic strategies, such as the one studied in this trial, will ultimately improve the outcomes for children with neuroblastoma,” Metelitsa concluded in a press statement.

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