Combining B7-H3 CAR T cells and ONC206 for the treatment of DIPG
Timpanaro A, Song EZ, Toumi R, et al. Preclinical Efficacy of Combinatorial B7-H3 CAR T Cells and ONC206 Against Diffuse Intrinsic Pontine Glioma. Neuro-Oncology. 2026; (doi: 10.1093/neuonc/noag025).
Chimeric antigen receptor (CAR) T cells targeting B7-H3 show promise in treating diffuse intrinsic pontine glioma (DIPG), but researchers suspect the true potential of this approach will only be unlocked by pairing this approach with another intervention. Preclinical study revealed favorable but inconsistent benefit, signaling that a multi-agent strategy might be necessary to achieve meaningful results against the rare but aggressive and deadly pediatric brain tumor. The team coupled B7-H3 CAR T cells with ONC206, an experimental imipridone molecule, and tested the combination across several DIPG cell cultures and orthotopic xenograft mouse models. B7-H3 CAR T alone induced robust cytotoxicity, and ONC206 led to mitochondrial dysfunction against DIPG cells. Together, low effector-to-target ratios of B7-H3 CAR T cells and IC50 concentrations of ONC206 boosted levels of IL-2, IL-29, VEGF-A, and Granzyme B and substantially improved cytotoxicity in vitro. In vivo, the method prolonged survival in DIPG xenograft mouse models.