Research And Grants

Augmentation of the tumor immune microenvironment to enhance B7-H3 CAR T cell efficacy against diffuse midline glioma

Diffuse midline glioma (DMG) is an aggressive, incurable pediatric brain tumor requiring new therapies. CAR T cells are a targeted immunotherapy in which some of a patient’s white blood cells are removed, engineered to fight a specific cancer target, and then returned to seek out the tumor. Seattle Children’s and St. Jude have each opened Phase 1 clinical trials of B7-H3 CAR T cells delivered intracranially to children with DMG. While St. Jude’s trial is ongoing, Seattle Children’s completed their trial and found a median survival of over 19 months (compared to the historical 11.2 months) with 3 patients now alive 51, 52, and 59 months from diagnosis. While these results are encouraging, not all children have benefited – likely due to the tumor’s immune microenvironment that opposes the activity of CAR T cells. Here, two leading cellular therapy programs will come together to define the best treatment that can be given prior to CAR T cells, with the aim of disrupting the tumor’s local immune environment to pave a path for CAR T cells to be most effective. Ultimately, this work will define the best treatment regimen prior to CAR T cells and define future clinical trials.