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Seattle Children's Studying CAR T-Cell Therapy Targeting Four Brain Cancer Antigens at Once

NEW YORK – Seattle Children's Therapeutics said on Tuesday that it has launched the BrainChild-04 trial of autologous, multi-antigen-targeting CAR T-cell therapy for pediatric, teenage, and young adult brain cancer patients. 

The trial will enroll 72 patients with diffuse intrinsic pontine glioma (DIPG), diffuse midline glioma, or recurrent or refractory central nervous system tumors. The first three patients enrolled must be over the age of 12, after which Seattle Children's will enroll patients between the ages of 1 and 26.

The autologous cell therapy, dubbed SC-CAR4BRAIN, involves patients' harvested CD4-positive and CD8-positive T cells engineered to express chimeric antigen receptors that simultaneously target four tumor antigens: B7-H3, EGFR806, HER2, and IL13-zetakine. The engineered product is delivered directly to patients' brains through a catheter.

Seattle Children's Therapeutics has evaluated the intracranial autologous CAR T-cell therapies targeting these individual tumor antigens, but it has never before tried to simultaneously target all four. The motivation behind targeting four antigens together is the heterogeneity of these tumors; their surfaces do not universally express the same antigens.

"We knew we would need to get to a CAR T-cell trial that could target more than one thing at a time," Nicholas Vitanza, the program lead for Seattle Children's Therapeutics BrainChild clinical trials, said in a statement. "The strategy was if we showed safety with the three different antigens targeted throughout the first three BrainChild trials, coupled with the existing adult data on the fourth antigen, we could initiate a CAR T-cell clinical trial that targets all four."

The primary goals of the trial involve evaluating SC-CAR4BRAIN's safety and manufacturing and administration feasibility as well as identifying its optimal dose.

According to Vitanza, the trial should also bring to light new information about how these brain and CNS tumors evolve.