Crystal L. Mackall (born August 21, 1960) is an American

physician A physician (American English), medical practitioner (Commonwealth English), medical doctor, or simply doctor, is a health professional who practices medicine, which is concerned with promoting, maintaining or restoring health through th ...

and immunologist. She is currently the Ernest and Amelia Gallo Family Professor of Pediatrics and Medicine at

Stanford University Stanford University, officially Leland Stanford Junior University, is a private research university in Stanford, California. The campus occupies , among the largest in the United States, and enrolls over 17,000 students. Stanford is consider ...

. She is the founding director of the Stanford Center for Cancer Cell Therapy.

Education and early career

Mackall grew up in

East Palestine, Ohio East Palestine ( ) is a village in northeastern Columbiana County, Ohio, United States. The population was 4,761 at the 2020 census. Located on the state's border with Pennsylvania, East Palestine is 20 miles (31 km) south of Youngstown and ...

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 The University of Akron is a public research university in Akron, Ohio. It is part of the University System of Ohio. As a STEM-focused institution, it focuses on industries such as polymers, advanced materials, and engineering. It is classified ...

and graduated

summa cum laude Latin honors are a system of Latin phrases used in some colleges and universities to indicate the level of distinction with which an academic degree has been earned. The system is primarily used in the United States. It is also used in some Sou ...

. She completed her medical education at

Northeast Ohio Medical University Northeast Ohio Medical University (NEOMED) is a public medical school in Rootstown, Ohio. It specializes in graduate education in medicine and pharmacy but also has a College of Graduate Studies. Its medical school has partnerships with four pu ...

, earning her

Doctor of Medicine Doctor of Medicine (abbreviated M.D., from the Latin language, Latin ''Medicinae Doctor'') is a medical degree, the meaning of which varies between different jurisdictions. In the United States, and some other countries, the M.D. denotes a profes ...

in 1984. She was a member of the

Alpha Omega Alpha Alpha Omega Alpha Honor Medical Society () is an honor society in the field of medicine. Alpha Omega Alpha currently has active Chapters in 132 LCME- accredited medical schools in the United States and Lebanon. It annually elects over 4,000 new ...

honour society. Mackall completed an internal medicine and

pediatrics Pediatrics ( also spelled ''paediatrics'' or ''pædiatrics'') is the branch of medicine that involves the medical care of infants, children, adolescents, and young adults. In the United Kingdom, paediatrics covers many of their youth until th ...

Residency at

Cleveland Clinic Akron General Cleveland Clinic Akron General formerly known as Akron General Medical Center, and commonly known as Akron Gen, is a nationally ranked, 511-bed non-profit, teaching hospital located in Akron, Ohio. Cleveland Clinic Akron General is a part of the Cle ...

and Children's Hospital of Akron in 1988. In 1989, Mackall joined the

National Cancer Institute The National Cancer Institute (NCI) coordinates the United States National Cancer Program and is part of the National Institutes of Health (NIH), which is one of eleven agencies that are part of the U.S. Department of Health and Human Services. ...

as a fellow in

pediatric oncology Childhood cancer is cancer in a child. About 80% of childhood cancer cases can be successfully treated thanks to modern medical treatments and optimal patient care. However, only about 10% of children diagnosed with cancer reside in high-income cou ...

, where she began to focus on

immunotherapy Immunotherapy or biological therapy is the treatment of disease by activating or suppressing the immune system. Immunotherapies designed to elicit or amplify an immune response are classified as ''activation immunotherapies,'' while immunotherap ...

for cancer. She remained at

National Institutes of Health The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late ...

until 2016, eventually serving as the Chief of the Pediatric Oncology Branch. She moved to the

Stanford University School of Medicine Stanford University School of Medicine is the medical school of Stanford University and is located in Stanford, California. It traces its roots to the Medical Department of the University of the Pacific, founded in San Francisco in 1858. This ...

in 2016. She is Board Certified in Internal Medicine, Pediatrics, and Pediatric Hematology/Oncology.

Research

Mackall has pioneered cancer immunotherapies for children. Her early research defined the effects of traditional cancer therapies on the immune system, where she identified the role of the

thymus The thymus is a specialized primary lymphoid organ of the immune system. Within the thymus, thymus cell lymphocytes or ''T cells'' mature. T cells are critical to the adaptive immune system, where the body adapts to specific foreign invaders. ...

in human

T cell A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell r ...

regeneration and discovered that

Interleukin Interleukins (ILs) are a group of cytokines (secreted proteins and signal molecules) that are expressed and secreted by white blood cells (leukocytes) as well as some other body cells. The human genome encodes more than 50 interleukins and related ...

-7 (IL-7) is the main regulator of

homeostasis in humans. Her group was among the first to demonstrate impressive activity of CD19 chimeric antigen receptor (

CAR T cells In biology, chimeric antigen receptors (CARs)—also known as chimeric immunoreceptors, chimeric T cell receptors or artificial T cell receptors—are receptor proteins that have been engineered to give T cells the new ability to target a specific ...

) 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. 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. 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 vaccine A cancer vaccine is a vaccine that either treats existing cancer or prevents development of cancer. Vaccines that treat existing cancer are known as ''therapeutic'' cancer vaccines or tumor antigen vaccines. Some of the vaccines are "autologous", ...

s, 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 In biology, chimeric antigen receptors (CARs)—also known as chimeric immunoreceptors, chimeric T cell receptors or artificial T cell receptors—are receptor proteins that have been engineered to give T cells the new ability to target a specific ...

(CAR-T) to identify

B-cell prolymphocytic leukemia B-cell prolymphocytic leukemia, referred to as B-PLL, is a rare blood cancer. It is a more aggressive, but still treatable, form of leukemia. Specifically, B-PLL is a prolymphocytic leukemia (PLL) that affects prolymphocytes – immature forms ...

and

B-cell lymphoma The B-cell lymphomas are types of lymphoma affecting B cells. Lymphomas are "blood cancers" in the lymph nodes. They develop more frequently in older adults and in immunocompromised individuals. B-cell lymphomas include both Hodgkin's lympho ...

. 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

peptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. A ...

s, antigen receptors and T cell fitness enhancements. She has served on the

editorial board The editorial board is a group of experts, usually at a publication, who dictate the tone and direction the publication's editorial policy will take. Mass media At a newspaper, the editorial board usually consists of the editorial page editor, a ...

s of several cancer journals, including '' Cancer Today''.

Awards and honors

* 2000

Distinguished Clinical Teacher Award * 2003, 2010

Director's Award * 2005

American Society for Clinical Investigation The American Society for Clinical Investigation (ASCI), established in 1908, is one of the oldest and most respected medical honor societies in the United States. Organization and purpose The ASCI is an honorary society to which more than 2,800 ph ...

Member * 2006-2018 Best Doctors in America Member * 2012

Great Teacher Lectureship * 2013

Children's Hospital of Philadelphia The Children's Hospital of Philadelphia (CHOP) is a children's hospital in Philadelphia, Pennsylvania, with its primary campus located in the University City neighborhood of West Philadelphia in the campus of the University of Pennsylvania. The h ...

Alexandra Scott Lectureship in Pediatric Oncology * 2013

Director's Award * 2015

G. Burroughs Mider Lectureship * 2017

MD Anderson Cancer Center The University of Texas MD Anderson Cancer Center (colloquially MD Anderson Cancer Center) is a comprehensive cancer center in Houston, Texas. It is the largest cancer center in the U.S. and one of the original three comprehensive cancer centers ...

Warren Sutow Distinguished Lectureship * 2018 Top 10 Clinical Research Award for New CAR-T Cell Therapy for Relapsed Leukemia * 2019

American Academy of Dermatology The American Academy of Dermatology (AAD) is a non-profit professional organization of dermatologists in the United States and Canada, based in Rosemont, Illinois, near Chicago. It was founded in 1938 and has more than 20,500 members. The Academy ...

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

Personal life

She identifies as LGBT and is married to Catherine L. Salem MD. The two have two sons, Theo Salem-Mackall and Zachary Salem-Mackall.

References

{{DEFAULTSORT:Mackall, Crystal American women physicians Cancer researchers Stanford University faculty University of Akron alumni 1960 births Living people American LGBT scientists American women scientists 21st-century LGBT people 21st-century American women