Dr. Crystal Mackall, Catapult Award Project: CAR T-cell Therapy DIPG

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Crystal Mackall, MD

Stanford University 

CureSearch Catapult Award: 2019-2022 

Focus: Diffuse intrinsic pontine glioma 

Project Title: GD2-CAR T-cells for H3K27M diffuse intrinsic pontine gliomas

Crystal Mackall, MD

Crystal Mackall, MD, will lead a novel trial examining GD2 CAR T-cell therapy as an approach to treat diffuse intrinsic pontine glioma (DIPG), a highly aggressive brain tumor in children that has a 5-year survival rate of less than 1%. 

Mackall is a professor of pediatrics and of medicine at the Stanford University School of Medicine, where she leads the Cancer Immunology and Immunotherapy Program, serves as associate director of the Stanford Cancer Institute and is the director of the Parker Institute for Cancer Immunotherapy (PICI) at Stanford. 

Project Update: As of November 2022, Dr. Mackall’s team conducted large-scale genomic testing in human CAR-T cells to identify specific genes that limit T cell function. They identified two genes, MED12 and CCNC, that were found to be key regulators of T-cell activation and the immune response. When these two genes were genetically inactivated in CAR-T cells, there was an increase in T-cell expansion, metabolic fitness, and tumor control. Technologies to inactivate genes are increasingly accessible, highlighting the potential for clinical translation of these findings. 

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