During a 27 year tenure culminating as Chief of the Pediatric Oncology Branch, NCI, and now through the Mackall Lab at Stanford (https://med.stanford.edu/mackalllab.html), Crystal L Mackall has led an internationally recognized translational research program focused on immunooncology. She has conducted numerous early phase and 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 and discovering IL-7 as the master regulator of T cell homeostasis. Her group was among the first to demonstrate impressive activity of CD19-CAR in pediatric leukemia, developed a novel CD22-CAR with impressive activity in leukemia refractory to CD19 targeting and identified T cell exhaustion as a major feature limiting the activity of CAR T cells. Recently her group has developed a novel approach to prevent human T cell exhaustion. Dr. Mackall’s clinical trials are notable for incorporation of deep biologic endpoints that further our understanding of the basis for success and failure of novel immunotherapeutics. She is a member of the American Society of Clinical Investigation, the Americal Academy of Physicians and received the Lila and Murray Gruber Award for Cancer Research in 2019. She serves in numerous national leadership positions, including co-PI on the NCI Pediatric Cancer Immunotherapy Network (U54), Leader of the NCI Pediatric Cancer Immunotherapy Trials Network, and co-Leader of the St. Baldrick’s-StandUp2Cancer Pediatric Dream Team. She is Board Certified in Pediatrics, Pediatric Hematology-Oncology and Internal Medicine.

Clinical Focus

• Pediatric Hematology-Oncology

Academic Appointments

• Professor, Pediatrics - Hematology & Oncology

• Professor, Medicine - Blood & Marrow Transplantation

• Member, Bio-X

• Member, Maternal & Child Health Research Institute (MCHRI)

• Member, Stanford Cancer Institute

Administrative Appointments

• Founding Director, Stanford Center for Cancer Cell Therapy (2017 - Present)

• Director, Parker Institute for Cancer Immunotherapy at Stanford (2016 - Present)

• Associate Director, Stanford Cancer Institute (2016 - Present)

• Leader, Cancer Immunology and Immunotherapy Program, Stanford Cancer Institute (2016 - Present)

• Director, Cancer Immunotherapy Program, Department of Pediatrics (2016 - Present)

Honors & Awards

• Lila and Murray Gruber Memorial Cancer Research Award and Lectureship, American Academy of Dermatology (March 2018)

• BJ Kennedy Keynote Lecturer, Masonic Cancer Center, Minneapolis, MN (2018)

• Top 10 Clinical Research Award for New CAR-T Cell Therapy for Relapsed Leukemia, Top 10 Clinical Research Award (2018)

• Chair, Pediatric Cancer Working Group, American Association for Cancer Research (2017-18)

• Stephen Max Memorial Lectureship, University of Maryland (2017)

• Advisory Board for Clinical Research, NIH Clinical Center (2008 - 2012)

• Vice Chair and Chair, Scientific Committee on Immunology and Host Defense, American Society of Hematology (2011 - 2012)

• Member, Immunology Steering Committee, American Association for Cancer Research (2013 - 2014)

• Chair, Program Committee on Immunology, American Association for Cancer Research (2014 - 2015)

• Chair-Elect, Pediatric Cancer Working Group, American Association for Cancer Research (2015 - 2017)

• Member, Committee on Scientific Affairs, American Society of Hematology (2016 - 2017)

• Chair, Pediatric Cancer Working Group, American Association for Cancer Research (2017 - Present)

Boards, Advisory Committees, Professional Organizations

• Executive Board, Federation of Clinical Immunology Societies (FOCIS) (2001 - 2002)

• Member, Biologic Response Modifiers Advisory Committee, Food and Drug Administration (2002 - 2003)

• Member, NIH Central Tenure Committee (2004 - 2008)

• Education Committee, American Society of Clinical Oncology (2006 - 2009)

• Member, DNA Advisory Committee, US Food and Drug Administration (2008 - 2008)

• Advisory Board for Clinical Research, NIH Clinical Center (2008 - 2012)

• Vice Chair and Chair, Scientific Committee on Immunology and Host Defense, American Society of Hematology (2011 - 2012)

• Member, Immunology Steering Committee, American Association for Cancer Research (2013 - 2014)

• Chair, Program Committee on Immunology, American Association for Cancer Research (2014 - 2015)

• Chair-Elect, Pediatric Cancer Working Group, American Association for Cancer Research (2015 - 2017)

• Member, Committee on Scientific Affairs, American Society of Hematology (2016 - 2017)

• Chair, Pediatric Cancer Working Group, American Association for Cancer Research (2017 - Present)

Professional Education

• Board Certification: Pediatrics, American Board of Pediatrics (1989)

• Board Certification: Pediatric Hematology-Oncology, American Board of Pediatrics (2017)

• Fellowship: National Cancer Institute - Center Cancer Research (1992) MD

• Board Certification: Internal Medicine, American Board of Internal Medicine (1989)

• Residency: Akron General Hospital (1988) OH

• MD, Northeastern Ohio Universities College of Medicine, Medicine (1984)

• Medical Education: Northeastern Ohio Universities (1984) OH

• BS, University of Akron, Natural Sciences (1980)

Current Research and Scholarly Interests

• We are impressed by the potency of T cell immune responses for the treatment of cancer and our work focuses on enhancing the effectiveness of T cell based immunotherapies for cancer. Our approach is to simultaneously conduct basic studies alongside clinical trials, leveraging an iterative bench-to-bedside-bench rotation to efficiently optimize clinically relevant cancer immunotherapies. Our laboratory seeks to develop novel therapies for early phase testing in clinical trials, and also conducts intensive studies on clinical samples obtained from patients treated on immunotherapy trials. We also seek to enhance fundamental understanding of human T cell biology.
  We focus primarily on using genetically engineered T cells to treat cancer, with an emphasis on chimeric antigen receptors (CARs). CARs are non-natural receptors, created using synthetic biology, that endow T cells with the capacity for antigen-specific, MHC-unrestricted killing. Some clinical results using CAR based therapies have been impressive, but we believe that further progress will emerge as a result of focus on these three major areas:
  1.T cell exhaustion, a state whereby continued T cell activation leads to diminished functionality, is a fundamental barrier limiting the efficacy of many cancer immunotherapies. Our laboratory is focused on using high dimensional, single cell analyses to better define human T cell exhaustion and to enhance understanding of the biological mechanisms responsible for this phenomena. We believe that enhanced understanding of T cell exhaustion will give rise to novel approaches to prevent or reverse this phenomenon in the context of cancer immunotherapy.
  2.Effective immunotherapies require a therapeutic window which allows the immune cell to preferentially or exclusively attack the neoplastic cell while sparing non-neoplastic, vital tissues. Our laboratory is focused on identifying novel targets for T cell based immunotherapies and for enhancing our understanding of the basis for differential antigen recognition using CAR T cells for cancer therapy. We are also interested in using novel approaches for combinatorial recognition, both to diminish the risk for tumor escape due to loss of antigen expression, and to allow targeting of tumor antigens that pose a risk due to co-expression on healthy, vital tissues.
  3.The tumor microenvironment is potently immunosuppressive and can prevent potent antigen specific immune responses from effectively mediating antitumor effects. Our laboratory focuses on enhancing understanding of the immunosuppressive tumor microenvironment and on developing novel approaches to diminish the ability of the tumor microenvironment to limit the efficacy of T cell based immunotherapies.

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