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Stephan Grupp

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Stephan Grupp
Academic background
EducationB.S. 1981, University of Cincinnati
Ph.D., 1985, MD, 1987, University of Cincinnati College of Medicine
ThesisMediators and modulators of the early B cell activation pathway (1985)
Academic work
InstitutionsChildren's Hospital of Philadelphia
Perelman School of Medicine at the University of Pennsylvania
Harvard Medical School
Main interestsCAR T-cell therapy

Stephan A. Grupp is an American pediatric oncologist. He is the Chief of the Cell Therapy and Transplant Section in the Division of Oncology and Director of the Cancer Immunotherapy Program at the Children's Hospital of Philadelphia and Professor of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania. In 2019, Grupp was elected a Member of the National Academy of Medicine.

He has led groundbreaking clinical trials of an innovative T-cell therapy for children with acute lymphoblastic leukemia (ALL). Grupp has developed the first highly effective childhood cancer immunotherapy and delivered CAR T-cell therapy to the first pediatric patient in the world. Grupp also helps lead trials on a CRISPR-based gene editing therapy for Sickle cell disease.[1]

Early life and education

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Grupp was born to German immigrant parents, both physicians, in the United States.[2] He earned his Bachelor of Science degree from the University of Cincinnati and his PhD in Immunology and medical degree from the University of Cincinnati College of Medicine. Following this, Grupp completed his Clinical Fellowship in Pediatrics at Harvard Medical School (Boston Children's Hospital) and his Clinical Fellowship in Pediatric Hematology/Oncology at the Dana-Farber/Boston Children's Cancer and Blood Disorders Center.[3]

Career

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Upon completing his formal education, Grupp accepted a faculty position at Harvard Medical School until 1996 when he joined the Children's Hospital of Philadelphia (CHOP).[4]

In 2017, Grupp was named chief of the section of cellular therapy and transplant within the division of oncology at CHOP.[5] While serving in this role, Grupp was honored as a Citizen Diplomat from the Citizen Diplomacy International for having "traveled throughout the world to teach doctors in other countries about using this therapy to treat children and young adults with acute lymphoblastic leukemia."[2]

Grupp was recognized by the National Academy of Medicine for "pioneering the development of an entirely novel therapy for acute lymphoblastic leukemia (ALL), and leading the first global engineered cell therapy trial that demonstrated effective sustained ALL remissions, making him a leader in cancer immunotherapy."[6] In the same year, he was also recognized by his alma mater with the Daniel Drake Award "for outstanding achievements in biomedical science as evidenced by major significant contributions to medical research or for a distinguished career as a clinician-teacher."[4] During the COVID-19 pandemic, Grupp collaborated with various researchers on "MIS-C different from severe COVID-19 in children." The study found that Multisystem inflammatory syndrome in children is a post-infectious syndrome distinct from Kawasaki disease and may help guide treatment decisions.[7]

T-cell therapy

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At CHOP, Grupp has led groundbreaking clinical trials of an innovative T-cell therapy for children with acute lymphoblastic leukemia (ALL). Pre clinical work began in the early 2000s, in addition to the first trials in activated T cell therapy. Clinical development in children began in 2011 when he received a $100,000 grant to continue his investigations on clinical trials for pediatric cancer research.[8] With this grant money, along with substantial funding from the Pennsylvania Department of Health, he began Phase 1 of the CART19 trial to study an innovative clinical trial that programs the immune system to attack blood cancers. The small number of children with B cell cancers would undergo have their T cells modified to attack specific types of cancer in their B cells.[9] In 2012, he performed the first pediatric CAR T-cell trial for acute lymphoblastic leukemia at CHOP and delivered CAR T-cell therapy to the first pediatric patient in the world.[10] He conducted the experimental T-cell therapy for advanced B-cell leukemias and lymphomas on seven year old Emily Whitehead, the first pediatric patient in the trial.[11] After attempting to use CTL019 therapy to treat her cancer, Whitehead became critically ill and was admitted to the intensive care unit. As a result, working with a team off scientists, Grupp injected her with a medication used to block the IL-6 receptor (tocilizumab) to treat this post-infusion illness (Cytokine release syndrome) which rapidly resolved her condition.[12][11]

Following the successful treatment of Whitehead, Grupp and his research team published their findings on two pediatric patients who had a complete remission of cancer following this treatment.[13] As a result of his medical achievements, Grupp was chosen by John M. Maris, director of the Center for Childhood Cancer Research at CHOP, to serve on the research team for his project "Immunogenomics to Create New Therapies for High-Risk Childhood Cancers."[14] He continued to work on personalized cellular therapy and in 2014, published findings that showed 90% of children and adults with ALL who had relapsed multiple times or failed to respond to standard therapies went into remission after receiving an investigational personalized cellular therapy (CTL019).[15] In recognition of his work, Grupp was the co-recipient of the Pennsylvania Bio’s Patient Impact Award[16] and Frank A. Oski Lectureship from the American Society of Pediatric Hematology/Oncology.[17]

In 2016, Grupp collaborated with colleagues in the Perelman School of Medicine at the University of Pennsylvania on their research study "CAR T Cell Therapy in Acute Lymphoblastic Leukemia and Potential for Chronic Lymphocytic Leukemia." In the study, they used immunotherapy to modify a patient’s own immune T cells. The scientists reported on the first global, multicenter clinical trial of these cells and on a separate single-center trial, the first to use a version of these cells carrying a “humanized” protein more similar to human proteins.[18][19] In recognition of his efforts, Grupp won 2016 Scientist of the Year from Philly Geek Awards.[20]

Following this, Grupp was the lead investigator of the Phase 2 trial regarding chimeric antigen receptor T (CAR-T) cell therapy which genetically modifies a patient’s immune cells to make them seek out and kill leukemia cells.[21] After Grupp oversaw five years of clinical trials, the Food and Drug Administration approved the use of CAR-T therapy for the treatment of relapsed or refractory pediatric and young adult patients with B-cell ALL.[22]

References

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  1. ^ "A cure for sickle cell disease is taking shape". {{cite journal}}: Cite journal requires |journal= (help)
  2. ^ a b "CHOP Pediatric Oncologist Honored as Citizen Diplomat". pjvoice.org. Philadelphia Jewish Voice. June 10, 2018. Retrieved February 14, 2021.
  3. ^ "Stephan A. Grupp". med.upenn.edu. Retrieved February 14, 2021.
  4. ^ a b "Daniel Drake Medal 2019". med.uc.edu. University of Cincinnati. 2019. Retrieved February 14, 2021.
  5. ^ "Children's Hospital of Philadelphia appoints section chief". healio.com. Healio. May 17, 2017. Retrieved February 14, 2021.
  6. ^ "Stephan Grupp, MD, PhD, Elected to the National Academy of Medicine". newswise.com. October 21, 2019. Retrieved February 14, 2021.
  7. ^ "MIS-C different from severe COVID-19 in children". sciencedaily.com. Science Daily. July 30, 2020. Retrieved February 14, 2021.
  8. ^ "Cookies for Kids Cancer Awards $200,000 to Oncology Research at The Children's Hospital of Philadelphia". PRWeb. May 13, 2011. Archived from the original on June 23, 2011. Retrieved February 14, 2021.
  9. ^ "CHOP Opens Clinical Trial for Pediatric Leukemia". chop.edu. October 17, 2011. Retrieved February 14, 2021.
  10. ^ "CAR-T Pioneer Dr. Stephan A. Grupp to Join Cellectis Clinical Advisory Board". cellectis.com. September 19, 2018. Retrieved February 14, 2021.
  11. ^ a b "Five Years Later, First Pediatric Recipient of CAR T-Cell Therapy Remains Cancer-free". chop.edu. July 12, 2017. Retrieved February 14, 2021.
  12. ^ "New Immune Cell Therapy Reverses an Aggressive ALL". chop.edu. February 5, 2013. Retrieved February 14, 2021.
  13. ^ "T-Cell Therapy Kills an Aggressive Leukemia in Two Children". chop.edu. March 25, 2013. Retrieved February 14, 2021.
  14. ^ "CHOP Oncologist Leads First Pediatric Dream Team". chop.edu. April 7, 2013. Retrieved February 14, 2021.
  15. ^ "Personalized Cellular Therapy Achieves Complete Remission in 90 Percent of Acute Lymphoblastic Leukemia Patients Studied". chop.edu. October 15, 2014. Retrieved February 14, 2021.
  16. ^ "The Children's Hospital of Philadelphia Honored with Pennsylvania Bio's Patient Impact Award". PRWeb. March 27, 2014. Retrieved February 14, 2021.
  17. ^ "2015 AWARD RECIPIENTS" (PDF). aspho.org. American Society of Pediatric Hematology/Oncology. 2015. p. 5. Retrieved February 14, 2021.
  18. ^ Singh, Nathan; Frey, Noelle E.; Grupp, Stephan A.; Maude, Shannon L. (June 2016). "CAR T Cell Therapy in Acute Lymphoblastic Leukemia and Potential for Chronic Lymphocytic Leukemia". Current Treatment Options in Oncology. 17 (6): 28. doi:10.1007/s11864-016-0406-4. PMID 27098534. S2CID 44503609. Retrieved February 14, 2021.
  19. ^ "In Clinical Trials, CAR T-Cell Immunotherapy Continues to Yield Complete Responses in Children & Young Adults with Relapsed and Refractory Leukemia". chop.edu. December 5, 2016. Retrieved February 14, 2021.
  20. ^ "STEPHAN GRUPP: Winner". phillygeekawards.com. Philly Geek Awards. Retrieved February 14, 2021.
  21. ^ "T-cell Therapy Pioneered at CHOP Shows Persistent Benefits in Young Leukemia Patients". chop.edu. February 1, 2018. Retrieved February 14, 2021.
  22. ^ "Immunotherapy: What's Next for CAR-T Therapy". chop.edu. January 24, 2019. Retrieved February 14, 2021.
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Stephan Grupp publications indexed by Google Scholar

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