Crystal Mackall
Crystal Mackall | |
---|---|
![]() Mackall at the National Cancer Institute in 2002 | |
Born | Crystal L. Mackall |
Alma mater | University of Akron Northeast Ohio Medical University |
Awards | National Institutes of Health Director's Award National Cancer Institute Director's Award |
Scientific career | |
Fields | Immunotherapy Chimeric antigen receptors Pediatric oncology T cell homeostasis[1] |
Institutions | Stanford University National Cancer Institute National Institutes of Health |
Website | profiles |
Crystal L. Mackall (born August 21, 1960) is an American physician and immunologist. She is currently the Ernest and Amelia Gallo Family Professor of Pediatrics and Medicine at Stanford University.[1][2] She is the founding director of the Stanford Center for Cancer Cell Therapy.
Education and early career
[edit]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.[3] 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.[3] In 1989, Mackall joined the National Cancer Institute as a fellow in pediatric oncology, where she began to focus on immunotherapy for cancer.[4][5] She remained at National Institutes of Health until 2016, eventually serving as the Chief of the Pediatric Oncology Branch.[6] She moved to the Stanford University School of Medicine in 2016.[6] She is Board Certified in Internal Medicine, Pediatrics, and Pediatric Hematology/Oncology.[7][8]
Research
[edit]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.[8][9] 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.[10][11] The CD22-CAR developed by Mackall's team is also active in large B cell lymphoma[12] 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,[13] and her group demonstrated that intracerebroventricular delivery of CAR T cells is more potent for treatment of brain tumors in mice than intravenous delivery.[14] Mackall and Monje are leading a clinical trial of GD2-CAR for diffuse midline gliomas, given intravenously and intracerebroventricularly, that has shown clinical activity.[15]
Mackall has elucidated fundamental biology related to T cells, with a focus on T cell exhaustion, demonstrating that cJUN overexpression prevents T cell exhaustion[16] and this work led to the launch of Lyell Immunopharma[17] which is testing this approach in clinical trials. Her group demonstrated that T cell exhaustion can be reversed by transient T cell rest[18] and demonstrated that dasatinib,[19] 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.[20] Mackall has led clinical trials of cancer vaccines,[21][22][23] launched the first clinical trial of recombinant human interleukin-7,[24][25] led studies of immune checkpoint inhibitors in pediatric cancers[26][27] and studied a role for bone marrow transplants in pediatric solid tumors.[28][29] 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.[30] 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.[30][31] 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.[32]
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
[edit]- 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[33]
- 2019 American Academy of Dermatology Lila and Murray Gruber Memorial Cancer Research Award[34]
- 2021 AACR-St. Baldrick’s Foundation Award for Outstanding Achievement in Pediatric Cancer Research[35]
- 2021 AACR Team Science Award to the St. Baldrick’s-StandUp2Cancer Team[36]
- 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”[37]
- 2021 American Society for Clinical Oncology Pediatric Oncology Award and Lecture[38]
- 2022 Fellow, American Association for Cancer Research[39]
- 2022 Nobility in Science Award, Sarcoma Foundation of America[40]
- 2022 National Academy of Medicine[41]
Personal life
[edit]She identifies as LGBT and is married to Catherine L. Salem MD. The two have two sons, Theo Salem-Mackall and Zachary Salem-Mackall.[42]
References
[edit]- ^ a b Crystal Mackall publications indexed by Google Scholar
- ^ Lee, Daniel W; Kochenderfer, James N; Stetler-Stevenson, Maryalice; Cui, Yongzhi K; Delbrook, Cindy; Feldman, Steven A; Fry, Terry J; Orentas, Rimas; Sabatino, Marianna; Shah, Nirali N; Steinberg, Seth M; Stroncek, Dave; Tschernia, Nick; Yuan, Constance; Zhang, Hua; Zhang, Ling; Rosenberg, Steven A; Wayne, Alan S; Mackall, Crystal L (2015). "T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial". The Lancet. 385 (9967): 517–528. doi:10.1016/S0140-6736(14)61403-3. ISSN 0140-6736. PMC 7065359. PMID 25319501.
- ^ a b "Crystal L. Mackall, MD". aacr.org. Archived from the original on 2019-06-17. Retrieved 2019-06-17.
- ^ "Crystal L. Mackall, MD". aacr.org. Archived from the original on 2019-06-17. Retrieved 2019-06-17. [verification needed]
- ^ "Crystal Mackall". stanfordhealthcare.org. Archived from the original on 2019-06-17. Retrieved 2019-06-17. [verification needed]
- ^ a b "Crystal Mackall, MD". parkerici.org. Parker Institute for Cancer Immunotherapy. Retrieved 2019-06-17. [verification needed]
- ^ "Crystal Mackall". stanfordhealthcare.org. Archived from the original on 2019-06-17. Retrieved 2019-06-17.
- ^ a b "Crystal Mackall, MD". parkerici.org. Parker Institute for Cancer Immunotherapy. Retrieved 2019-06-17.
- ^ "Immunotherapy Expert Crystal Mackall, MD, Joins Stanford Medicine Faculty - The ASCO Post". ascopost.com. Retrieved 2019-06-17.
- ^ Fry, Terry J; Shah, Nirali N; Orentas, Rimas J; Stetler-Stevenson, Maryalice; Yuan, Constance M; Ramakrishna, Sneha; Wolters, Pamela; Martin, Staci; Delbrook, Cindy (2018). "CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy". Nature Medicine. 24 (1): 20–28. doi:10.1038/nm.4441. ISSN 1078-8956. PMC 5774642. PMID 29155426.
- ^ "FDA grants breakthrough therapy designation for new CAR T-cell therapy for B-cell acute lymphoblastic leukemia". National Cancer Institute at the National Institutes of Health. September 10, 2019.
- ^ Baird, John H.; Frank, Matthew J.; Craig, Juliana; Patel, Shabnum; Spiegel, Jay Y.; Sahaf, Bita; Oak, Jean S.; Younes, Sheren F.; Ozawa, Michael G.; Yang, Eric; Natkunam, Yasodha; Tamaresis, John; Ehlinger, Zachary; Reynolds, Warren D.; Arai, Sally (2021-04-29). "CD22-directed CAR T-cell therapy induces complete remissions in CD19-directed CAR-refractory large B-cell lymphoma". Blood. 137 (17): 2321–2325. doi:10.1182/blood.2020009432. ISSN 1528-0020. PMC 8085484. PMID 33512414.
- ^ Mount, Christopher W.; Majzner, Robbie G.; Sundaresh, Shree; Arnold, Evan P.; Kadapakkam, Meena; Haile, Samuel; Labanieh, Louai; Hulleman, Esther; Woo, Pamelyn J.; Rietberg, Skyler P.; Vogel, Hannes; Monje, Michelle; Mackall, Crystal L. (May 2018). "Potent antitumor efficacy of anti-GD2 CAR T cells in H3-K27M+ diffuse midline gliomas". Nature Medicine. 24 (5): 572–579. doi:10.1038/s41591-018-0006-x. ISSN 1546-170X. PMC 6214371. PMID 29662203.
- ^ Theruvath, Johanna; Sotillo, Elena; Mount, Christopher W.; Graef, Claus Moritz; Delaidelli, Alberto; Heitzeneder, Sabine; Labanieh, Louai; Dhingra, Shaurya; Leruste, Amaury; Majzner, Robbie G.; Xu, Peng; Mueller, Sabine; Yecies, Derek W.; Finetti, Martina A.; Williamson, Daniel (May 2020). "Locoregionally administered B7-H3-targeted CAR T cells for treatment of atypical teratoid/rhabdoid tumors". Nature Medicine. 26 (5): 712–719. doi:10.1038/s41591-020-0821-8. ISSN 1546-170X. PMC 7992505. PMID 32341579.
- ^ Majzner, Robbie G.; Ramakrishna, Sneha; Yeom, Kristen W.; Patel, Shabnum; Chinnasamy, Harshini; Schultz, Liora M.; Richards, Rebecca M.; Jiang, Li; Barsan, Valentin; Mancusi, Rebecca; Geraghty, Anna C.; Good, Zinaida; Mochizuki, Aaron Y.; Gillespie, Shawn M.; Toland, Angus Martin Shaw (March 2022). "GD2-CAR T cell therapy for H3K27M-mutated diffuse midline gliomas". Nature. 603 (7903): 934–941. Bibcode:2022Natur.603..934M. doi:10.1038/s41586-022-04489-4. ISSN 1476-4687. PMC 8967714. PMID 35130560.
- ^ Lynn, Rachel C.; Weber, Evan W.; Sotillo, Elena; Gennert, David; Xu, Peng; Good, Zinaida; Anbunathan, Hima; Lattin, John; Jones, Robert; Tieu, Victor; Nagaraja, Surya; Granja, Jeffrey; de Bourcy, Charles F. A.; Majzner, Robbie; Satpathy, Ansuman T. (December 2019). "c-Jun overexpression in CAR T cells induces exhaustion resistance". Nature. 576 (7786): 293–300. Bibcode:2019Natur.576..293L. doi:10.1038/s41586-019-1805-z. ISSN 1476-4687. PMC 6944329. PMID 31802004.
- ^ "Pioneering Transformative T-Cell Therapies". Lyell. Retrieved 2022-12-30.
- ^ Weber, Evan W.; Parker, Kevin R.; Sotillo, Elena; Lynn, Rachel C.; Anbunathan, Hima; Lattin, John; Good, Zinaida; Belk, Julia A.; Daniel, Bence; Klysz, Dorota; Malipatlolla, Meena; Xu, Peng; Bashti, Malek; Heitzeneder, Sabine; Labanieh, Louai (2021-04-02). "Transient rest restores functionality in exhausted CAR-T cells through epigenetic remodeling". Science. 372 (6537): eaba1786. doi:10.1126/science.aba1786. ISSN 1095-9203. PMC 8049103. PMID 33795428.
- ^ Weber, Evan W.; Lynn, Rachel C.; Sotillo, Elena; Lattin, John; Xu, Peng; Mackall, Crystal L. (2019-03-12). "Pharmacologic control of CAR-T cell function using dasatinib". Blood Advances. 3 (5): 711–717. doi:10.1182/bloodadvances.2018028720. ISSN 2473-9537. PMC 6418502. PMID 30814055.
- ^ Freitas, Katherine A.; Belk, Julia A.; Sotillo, Elena; Quinn, Patrick J.; Ramello, Maria C.; Malipatlolla, Meena; Daniel, Bence; Sandor, Katalin; Klysz, Dorota; Bjelajac, Jeremy; Xu, Peng; Burdsall, Kylie A.; Tieu, Victor; Duong, Vandon T.; Donovan, Micah G. (2022-11-11). "Enhanced T cell effector activity by targeting the Mediator kinase module". Science. 378 (6620): eabn5647. doi:10.1126/science.abn5647. ISSN 1095-9203. PMC 10335827. PMID 36356142. S2CID 253458258.
- ^ Zhang, Hua; Chua, Kevin S.; Guimond, Martin; Kapoor, Veena; Brown, Margaret V.; Fleisher, Thomas A.; Long, Lauren M.; Bernstein, Donna; Hill, Brenna J.; Douek, Daniel C.; Berzofsky, Jay A.; Carter, Charles S.; Read, E. J.; Helman, Lee J.; Mackall, Crystal L. (November 2005). "Lymphopenia and interleukin-2 therapy alter homeostasis of CD4+CD25+ regulatory T cells". Nature Medicine. 11 (11): 1238–1243. doi:10.1038/nm1312. ISSN 1078-8956. PMID 16227988. S2CID 24773329.
- ^ Mackall, Crystal L.; Rhee, Eunice H.; Read, Elizabeth J.; Khuu, Hanh M.; Leitman, Susan F.; Bernstein, Donna; Tesso, Merertu; Long, Lauren M.; Grindler, David; Merino, Margret; Kopp, William; Tsokos, Maria; Berzofsky, Jay A.; Helman, Lee J. (2008-08-01). "A pilot study of consolidative immunotherapy in patients with high-risk pediatric sarcomas". Clinical Cancer Research. 14 (15): 4850–4858. doi:10.1158/1078-0432.CCR-07-4065. ISSN 1078-0432. PMC 2497450. PMID 18676758.
- ^ Merchant, Melinda S.; Bernstein, Donna; Amoako, Martha; Baird, Kristin; Fleisher, Thomas A.; Morre, Michel; Steinberg, Seth M.; Sabatino, Marianna; Stroncek, Dave F.; Venkatasan, Aradhana M.; Wood, Bradford J.; Wright, Matthew; Zhang, Hua; Mackall, Crystal L. (2016-07-01). "Adjuvant Immunotherapy to Improve Outcome in High-Risk Pediatric Sarcomas". Clinical Cancer Research. 22 (13): 3182–3191. doi:10.1158/1078-0432.CCR-15-2550. ISSN 1557-3265. PMC 7831150. PMID 26823601.
- ^ Sportès, Claude; Babb, Rebecca R.; Krumlauf, Michael C.; Hakim, Frances T.; Steinberg, Seth M.; Chow, Catherine K.; Brown, Margaret R.; Fleisher, Thomas A.; Noel, Pierre; Maric, Irina; Stetler-Stevenson, Maryalice; Engel, Julie; Buffet, Renaud; Morre, Michel; Amato, Robert J. (2010-01-15). "Phase I study of recombinant human interleukin-7 administration in subjects with refractory malignancy". Clinical Cancer Research. 16 (2): 727–735. doi:10.1158/1078-0432.CCR-09-1303. ISSN 1557-3265. PMC 2808195. PMID 20068111.
- ^ Sportès, Claude; Hakim, Frances T.; Memon, Sarfraz A.; Zhang, Hua; Chua, Kevin S.; Brown, Margaret R.; Fleisher, Thomas A.; Krumlauf, Michael C.; Babb, Rebecca R.; Chow, Catherine K.; Fry, Terry J.; Engels, Julie; Buffet, Renaud; Morre, Michel; Amato, Robert J. (2008-07-07). "Administration of rhIL-7 in humans increases in vivo TCR repertoire diversity by preferential expansion of naive T cell subsets". The Journal of Experimental Medicine. 205 (7): 1701–1714. doi:10.1084/jem.20071681. ISSN 1540-9538. PMC 2442646. PMID 18573906.
- ^ Merchant, Melinda S.; Wright, Matthew; Baird, Kristin; Wexler, Leonard H.; Rodriguez-Galindo, Carlos; Bernstein, Donna; Delbrook, Cindy; Lodish, Maya; Bishop, Rachel; Wolchok, Jedd D.; Streicher, Howard; Mackall, Crystal L. (2016-03-15). "Phase I Clinical Trial of Ipilimumab in Pediatric Patients with Advanced Solid Tumors". Clinical Cancer Research. 22 (6): 1364–1370. doi:10.1158/1078-0432.CCR-15-0491. ISSN 1557-3265. PMC 5027962. PMID 26534966.
- ^ Davis, Kara L.; Fox, Elizabeth; Merchant, Melinda S.; Reid, Joel M.; Kudgus, Rachel A.; Liu, Xiaowei; Minard, Charles G.; Voss, Stephan; Berg, Stacey L.; Weigel, Brenda J.; Mackall, Crystal L. (April 2020). "Nivolumab in children and young adults with relapsed or refractory solid tumours or lymphoma (ADVL1412): a multicentre, open-label, single-arm, phase 1-2 trial". The Lancet. Oncology. 21 (4): 541–550. doi:10.1016/S1470-2045(20)30023-1. ISSN 1474-5488. PMC 7255545. PMID 32192573.
- ^ Baird, Kristin; Fry, Terry J.; Steinberg, Seth M.; Bishop, Michael R.; Fowler, Daniel H.; Delbrook, Cynthia P.; Humphrey, Jennifer L.; Rager, Alison; Richards, Kelly; Wayne, Alan S.; Mackall, Crystal L. (May 2012). "Reduced-intensity allogeneic stem cell transplantation in children and young adults with ultrahigh-risk pediatric sarcomas". Biology of Blood and Marrow Transplantation. 18 (5): 698–707. doi:10.1016/j.bbmt.2011.08.020. ISSN 1523-6536. PMC 3262116. PMID 21896345.
- ^ Shah, Nirali N.; Baird, Kristin; Delbrook, Cynthia P.; Fleisher, Thomas A.; Kohler, Mark E.; Rampertaap, Shakuntala; Lemberg, Kimberly; Hurley, Carolyn K.; Kleiner, David E.; Merchant, Melinda S.; Pittaluga, Stefania; Sabatino, Marianna; Stroncek, David F.; Wayne, Alan S.; Zhang, Hua (2015-01-29). "Acute GVHD in patients receiving IL-15/4-1BBL activated NK cells following T-cell-depleted stem cell transplantation". Blood. 125 (5): 784–792. doi:10.1182/blood-2014-07-592881. ISSN 1528-0020. PMC 4311226. PMID 25452614.
- ^ a b "Mackall awarded $11.9 million for anti-leukemia clinical trial". med.stanford.edu. 20 November 2017. Retrieved 2019-06-17.
- ^ Spiegel, Jay Y.; Patel, Shabnum; Muffly, Lori; Hossain, Nasheed M.; Oak, Jean; Baird, John H.; Frank, Matthew J.; Shiraz, Parveen; Sahaf, Bita; Craig, Juliana; Iglesias, Maria; Younes, Sheren; Natkunam, Yasodha; Ozawa, Michael G.; Yang, Eric (August 2021). "CAR T cells with dual targeting of CD19 and CD22 in adult patients with recurrent or refractory B cell malignancies: a phase 1 trial". Nature Medicine. 27 (8): 1419–1431. doi:10.1038/s41591-021-01436-0. ISSN 1546-170X. PMC 8363505. PMID 34312556.
- ^ cirm_2.0 (2022-12-30). "Phase 1 Clinical Trial of Autologous GD2 Chimeric Antigen Receptor T Cells for Diffuse Intrinsic Pontine Gliomas and Spinal Diffuse Midline Glioma". California's Stem Cell Agency. Retrieved 2022-12-30.
{{cite web}}
: CS1 maint: numeric names: authors list (link) - ^ "Crystal Mackall's Profile | Stanford Profiles". profiles.stanford.edu. Retrieved 2020-10-18.
- ^ "Lila and Murray Gruber Memorial Cancer Research Award and Lectureship". www.aad.org. Retrieved 2020-10-18.
- ^ "Ludwig Cancer Research". Retrieved 2022-12-30.
- ^ "AACR to Recognize the St. Baldrick's Foundation-Stand Up To Cancer Pediatric Cancer Dream Team with 2021 Team Science Award". American Association for Cancer Research (AACR). Retrieved 2022-12-30.
- ^ "SITC Smalley Award 2021 Recipient | Richard V. Smalley, MD Memorial Award". www.sitcancer.org. Retrieved 2022-12-30.
- ^ "Dr. Crystal L. Mackall Named Pediatric Oncology Award Recipient for Research in Immuno-Oncology". ASCO Daily News. 2021. doi:10.1200/ADN.21.200537. S2CID 243534420. Retrieved 2022-12-30.
- ^ "AACR Announces Fellows of the AACR Academy Class of 2022". American Association for Cancer Research (AACR). Retrieved 2022-12-30.
- ^ Saunders, Cindy (2022-08-30). "SFA Honors Crystal L. Mackall with 2022 Nobility in Science Award". Sarcoma Foundation of America. Retrieved 2022-12-30.
- ^ "Six professors elected to the National Academy of Medicine". News Center (in Samoan). 20 October 2021. Retrieved 2022-12-30.
- ^ "+OUTlist". Stanford Medicine. Retrieved 2020-10-18.
- American women physicians
- American cancer researchers
- Stanford University faculty
- University of Akron alumni
- 1960 births
- Living people
- American LGBT scientists
- American women scientists
- 21st-century American LGBT people
- 21st-century American women
- Members of the National Academy of Medicine
- Members of the American Society for Clinical Investigation
- Northeast Ohio Medical University alumni