Potent antitumor efficacy of anti-GD2 CAR T cells in H3-K27M⁺ diffuse midline gliomas.

ABSTRACT: Diffuse intrinsic pontine glioma (DIPG) and other diffuse midline gliomas (DMGs) with mutated histone H3 K27M (H3-K27M)^1-5 are aggressive and universally fatal pediatric brain cancers ⁶ . Chimeric antigen receptor (CAR)-expressing T cells have mediated impressive clinical activity in B cell malignancies^7-10, and recent results suggest benefit in central nervous system malignancies^11-13. Here, we report that patient-derived H3-K27M-mutant glioma cell cultures exhibit uniform, high expression of the disialoganglioside GD2. Anti-GD2 CAR T cells incorporating a 4-1BBz costimulatory domain ¹⁴ demonstrated robust antigen-dependent cytokine generation and killing of DMG cells in vitro. In five independent patient-derived H3-K27M⁺ D

SUBMITTER: Mount CW 

PROVIDER: S-EPMC6214371 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature