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 (IL-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 (
CAR T cells) 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 (CAR-T) 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 • 2000
National Institutes of Health Distinguished Clinical Teacher Award • 2003, 2010
National Cancer Institute Director's Award • 2005
American Society for Clinical Investigation Member • 2006-2018 Best Doctors in America Member • 2012
National Institutes of Health Great Teacher Lectureship • 2013
Children's Hospital of Philadelphia Alexandra Scott Lectureship in Pediatric Oncology • 2013
National Institutes of Health Director's Award • 2015
National Institutes of Health G. Burroughs Mider Lectureship • 2017
MD Anderson Cancer Center Warren Sutow Distinguished Lectureship • 2018 Top 10 Clinical Research Award for New CAR-T Cell Therapy for Relapsed Leukemia • 2019
American Academy of Dermatology Lila and Murray Gruber Memorial Cancer Research Award • 2021 AACR-St. Baldrick's Foundation Award for Outstanding Achievement in Pediatric Cancer Research • 2021 AACR Team Science Award to the St. Baldrick's-StandUp2Cancer Team • 2021 Richard V. Smalley Award and Lectureship, The Society for the Immunotherapy of Cancer's "most prestigious award to a clinician/scientist and luminary in the field who has significantly contributed to the advancement of
cancer immunotherapy research" • 2021 American Society for Clinical Oncology Pediatric Oncology Award and Lecture • 2022 Fellow, American Association for Cancer Research • 2022 Nobility in Science Award, Sarcoma Foundation of America • 2022 National Academy of Medicine • 2023 George Stamatoyannopoulos Award Lecture, American Society for Gene and Cell Therapy • 2023 Top 20 Most Influential Women in Biopharma, Endpoints News • 2023 Fellow of the Academy of Immunooncology, Society for Immunotherapy of Cancer • 2023 Edward Netter Leadership Award, Alliance for Cancer Gene Therapy • 2024 Almanac of Women Leaders in Pediatric Oncology, International Society of Pediatric Oncology • 2024 R. Lois Murphy Award, Memorial Sloan Kettering Cancer Center == Personal life ==