Intrinsic target

Diffuse intrinsic pontine glioma (DIPG) and other H3K27M-mutated diffuse midline gliomas tend to weave into brain tissue and are uniformly and swiftly lethal. Ludwig Stanford investigators Michelle Monje and Crystal Mackall reported in a February paper in Nature promising findings from a phase 1 clinical trial testing a CAR-T cell therapy they devised in four patients with H3K27M-mutant DIPG/DMG. Michelle’s lab collaborated with Crystal’s to show in 2018 that CAR-T cells directed against the GD2 antigen expressed by such tumors could clear DIPG in mouse models. In the current trial, three of the four patients with advanced midline gliomas exhibited unprecedented clinical and radiological benefits from the therapy, and the anticipated side effect of brain inflammation could be managed with intensive care. Those who responded to the intravenous transfusions of GD2-targeting CAR-T cells received additional infusions through an Ommaya catheter threaded into the ventricular system of the brain, which also relieved potentially deadly pressure from the inflammation. The researchers subsequently reported at the AACR Annual Meeting in April that sequential intravenous and cerebroventricular delivery in another set of patients induced dramatic tumor regressions in the ongoing clinical trial. For more on the background story of this study, check out our profile of Michelle and our Q&A with her.


This article appeared in the May 2022 issue of Ludwig Link. Click here to download a copy (PDF, 2MB).


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