Diffuse implications.

Top Line: Diffuse intrinsic pontine glioma (DIPG) is a universally fatal disease.

The Study: Recent reporting of a small feasibility study (n=12) established the relative safety of intratumoral injection of an oncolytic virus—safe relative to rapid progression of a brainstem tumor. While 85% of DIPG is H3K27M-altered and currently reclassified as diffuse midline glioma, nearly 100% expresses B7-H3 (CD276) an immunoregulatory member of the B7 protein family that, by the way, is also universally expressed by atypical teratoid rhabdoid tumor (ATRT), medulloblastoma, and high-grade glioma. So an ingenious group at the University of Washington decided to harness the power for CAR T-cells primed with specificity for this B7-H3. This first-in-human phase 1 trial used such therapy on three children with refractory DIPG with plenty of basic science goodies. CAR T-cells were manufactured in established ways and delivered via CNS catheters every other week for 40 infusions (thus far) with no dose-limiting toxicity at time of reporting. One patients acheived clinical and radiographic improvement ongoing at 12 months, a second has stable disease at 16 months, and the third has progressive disease at 12 months. The basic science part comes in to demonstrate the cerebrospinal fluid of these patients did indeed have multiple demonstrable increased markers of an immune response.

TBL: Serial intracranial delivery via CNS catheter of CAR T-cells primed for a DIPG-specific marker B7-H3 is promising and may signal the first novel treatment paradigm this devastating disease has seen in decades. | Vitanza, Cancer Discov 2023