Scientist Stories: Crystal Mackall, Pioneer in Immune Cell Exhaustion and Cell Therapies
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 Published On Oct 4, 2022

Crystal L Mackall MD is the Ernest and Amelia Gallo Family Professor of Pediatrics and Medicine at Stanford University, the Founding Director of the Stanford Center for Cancer Cell Therapy, Associate Director of the Stanford Cancer Institute, Leader of the Cancer Immunotherapy Program and Director of the Parker Institute for Cancer Immunotherapy @ Stanford. During a 27-year tenure at NCI culminating as Chief of the Pediatric Oncology Branch and Head of the Immunology Section and since 2016 at Stanford, she has led an internationally recognized translational research program focused on immune-oncology. Her work has advanced understanding of fundamental immunology and translated this understanding for the treatment of human disease with a major focus on children’s cancers. She has led numerous first-in-human and first-in-child clinical trials spanning dendritic cell vaccines, cytokines, and adoptive immunotherapy using NK cells and genetically modified T cells. Her work is credited with identifying an essential role for the thymus in human T cell regeneration (NEJM 1995) and discovering IL-7 as the master regulator of T cell homeostasis (Blood 2001, J Exp Med 2008). Her group was among the first to demonstrate impressive activity of CD19-CAR in pediatric leukemia (Lancet 2015), developed a CD22-CAR that is the only active salvage therapy for CAR19 resistant B cell malignancies (Nat Med 2018, J Clin Onc 2020, Blood 2021), demonstrated preclinical activity of GD2 targeting CARs for pediatric diffuse intrinsic pontine glioma (Nat Med 2018), demonstrated superiority of regional CNS delivery of CAR T cells for brain tumors (Nat Med 2020) and demonstrated impressive clinical activity of GD2-CAR T cells in this disease (NCT04196413), which is among the first to demonstrate significant and consistent activity of CAR T cells in solid cancers (Nature 2022). Her group identified T cell exhaustion as a major feature CAR T cell potency (Nat Med 2015), created the first exhaustion-resistance (Nature 2019) and exhaustion-reversal platforms (Science 2021) and developed a best-in-class regulatable “remote-controlled” CAR T cell platform (Cell, 2022). She serves in numerous national leadership positions, including Co-PI of a Pediatric Immunotherapy Discovery and Development Network U54 grant, and co-Leader of the St. Baldrick’s-StandUp2Cancer Pediatric Dream Team. She has received numerous awards, including election as a fellow of the AACR Academy, the Smalley Award for outstanding contributions to cancer immunotherapy from the Society for the Immunotherapy of Cancer, the AACR-St.Baldrick’s Distinguished Achievement Award for Pediatric Cancer Research, and the Nobility in Science Award from the Sarcoma Foundation of America. She has published over 250 manuscripts and her h-index in August 2022 according to google scholar is 96 and founded 3 biotech companies. Crystal is Board Certified in Pediatrics, Pediatric Hematology-Oncology and Internal Medicine.

https://en.wikipedia.org/wiki/Crystal...

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