Neuroblastoma is a type of cancer that affects the sympathetic nervous system’s immature nerve cells. In the United States, approximately 700 people are diagnosed with the tumor each year, the majority of them are kids aged 5 or younger. Despite rigorous treatment, approximately half of individuals with high-risk neuroblastoma die.

A St. Jude phase II clinical trial found that newly diagnosed patients who received the humanized monoclonal antibody hu14.18K322A in addition to standard therapy for high-risk illness had considerably greater survival rates. The study’s 64 kids had a three-year disease-free survival rate of 73.7 percent. The total survival rate was 86%.

“I have treated high-risk neuroblastoma for 30 years, and I have never seen results like this in high-risk patients,” says first and corresponding author Dr. Wayne Furman.

“This is the best result published to date for patients with high-risk neuroblastoma, period.”

If the findings are verified in a larger, multi-center clinical trial, Furman believes that the chemoimmunotherapy described in this study could become standard treatment for individuals with high-risk illnesses.

Hu14.18322A, an anti-GD2 monoclonal antibody with a twist, was created in the lab to bind GD2 antibodies on the surface of neuroblastoma tumor cells. The binding mobilizes immune cells to target and destroys tumor cells. The monoclonal antibody utilized in this trial was created in the Children’s GMP, LLC. laboratory on the St. Jude campus, using a procedure improved by scientists at the facility.

Hu14.18322A is not the first monoclonal antibody created for neuroblastoma treatment. Some normal tissue, including cells in the peripheral nervous system, contains GD2 antibodies. hu14.18322A, unlike other anti-GD2 monoclonal antibodies, is designed to alleviate dose-limiting discomfort and other therapy adverse effects.

hu14.18K322A was included in the phase II study throughout treatment. High-dose chemotherapy, immunotherapy with granulocyte-macrophage colony-stimulating factor and interleukin 2, surgery, autologous blood stem cell transplantation, and radiation were all part of the treatment. Patients were also given opioids to help with pain control. Combining hu14.18K322A with other immunotherapies and high-dose chemotherapy appears to have a synergistic impact, according to evidence from this and earlier research.

Dinutuximab was the first anti-GD2 monoclonal antibody approved by the FDA for the treatment of high-risk neuroblastoma.

Patients in the St. Jude phase II clinical trial were given much greater doses of hu14.18K322A, almost 2.5 times the maximum approved dose of dinutuximab.

“Since dinutuximab cannot be given at the same dose, one of the unanswered questions is whether the patient results in this study were so good because hu14.18K322A is a better antibody or because patients are receiving a higher dose,” said Furman.

Source: JCO.21.01375R2

Image Credit: Getty

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