Crystal Mackall


Crystal L. Mackall is an American physician and immunologist. She is currently the Ernest and Amelia Gallo Family Professor of Pediatrics and Medicine at Stanford University. She is the founding director of the Stanford Center for Cancer Cell Therapy.

Education and early career

Mackall grew up in East Palestine, Ohio in a working-class family; her father was a steelworker. She received her medical training through a six-year BS/MD program, earning her bachelor's degree at the University of Akron and graduated summa cum laude. She completed her medical education at Northeast Ohio Medical University, earning her Doctor of Medicine in 1984. She was a member of the Alpha Omega Alpha honour society. Mackall completed an internal medicine and pediatrics Residency at Cleveland Clinic Akron General and Children's Hospital of Akron in 1988. In 1989, Mackall joined the National Cancer Institute as a fellow in pediatric oncology, where she began to focus on immunotherapy for cancer.  She remained at National Institutes of Health until 2016, eventually serving as the Chief of the Pediatric Oncology Branch.  She moved to the Stanford University School of Medicine in 2016.  She is Board Certified in Internal Medicine, Pediatrics, and Pediatric Hematology/Oncology.

Research

Mackall has pioneered cancer immunotherapies with a major focus on children's cancers. Her early research defined the effects of traditional cancer therapies on the immune system, where she identified the role of the thymus in human T cell regeneration and discovered that Interleukin-7 is the main regulator of T cell homeostasis in humans. Her group was among the first to demonstrate impressive activity of CD19 chimeric antigen receptor therapies for childhood leukemia and also developed a CAR targeting CD22 that is active in this disease and has received Breakthrough Therapy Designation from the US FDA for treatment of CAR19 refractory B-ALL. The CD22-CAR developed by Mackall's team is also active in large B cell lymphoma and has received Breakthrough Therapy Designation from the US FDA for this indication. Mackall co-founded CARGO Therapeutics to commercialize the CD22-CAR, now named Firi-cel, which is undergoing Phase II testing in a potentially pivotal trial for patients with large B cell lymphoma.
Working with the Monje lab at Stanford, Mackall developed a GD2-CAR that showed activity in preclinical models of diffuse midline glioma, which are lethal brain tumor occurring primarily in children and young adults, and her group demonstrated that intracerebroventricular delivery of CAR T cells is more potent for treatment of brain tumors in mice than intravenous delivery. Mackall and Monje are leading a clinical trial of GD2-CAR for diffuse midline gliomas, given intravenously and intracerebroventricularly, that has shown clinical activity. Based on this work, the FDA has designated the GD2-CAR therapy a Regenerative Medicine Advanced Therapeutic and Mackall is leading efforts to commercialize this therapy through ACCESSforKIDS, a non-profit advanced medicine biotech focused on delivering cell therapies for pediatric diseases.
Mackall has elucidated fundamental biology related to T cells, with a focus on T cell exhaustion, demonstrating that cJUN overexpression prevents T cell exhaustion and this work led to the launch of Lyell Immunopharma which is testing this approach in clinical trials. Her group demonstrated that T cell exhaustion can be reversed by transient T cell rest and demonstrated that dasatinib, a commonly prescribed oral drug, could be used to rest human T cells. Mackall and Freitas discovered a role for the mediator kinase modules in regulating T cell effector differentiation and demonstrated that MED12 knockout increased the potency of human T cells in preclinical models. Mackall has led clinical trials of cancer vaccines, launched the first clinical trial of recombinant human interleukin-7, led studies of immune checkpoint inhibitors in pediatric cancers and studied a role for bone marrow transplants in pediatric solid tumors. In 2018 Mackall was awarded $11.9 million from the California Institute of Regenerative Medicine to lead a clinical trial using genetically modified T cells engineered to recognize CD19 or CD22 proteins expressed on leukemia or lymphoma. The trial was conducted at the Stanford Center for Cancer Cell Therapy, which modified the chimeric antigen receptor T cell to identify B-cell prolymphocytic leukemia and B-cell lymphoma. In 2022, Mackall was awarded $11.9 million from the California Institute of Regenerative Medicine to lead a clinical trial using T cells engineered to express GD2-CAR T cells for treatment of diffuse midline gliomas.
Mackall holds a number of patents relating to peptides, antigen receptors and T cell fitness enhancements. She has served on the editorial boards of several cancer journals, including Cancer Today.

Awards and honors

Mackall is a member of the LGBTQ+ community.