![Stephan A. Grupp, MD, PhD](/sites/default/files/styles/crop_and_center_300x375/public/providers-new-grupp-stephan.jpg?itok=UfUHGCdm)
Stephan A. Grupp, MD, PhD
Areas of expertise: Bone marrow transplant, Development of engineered T cell therapies such as CAR T for cancer and gene-modified stem cells for sickle cell disease, Transplant for high-risk neuroblastoma
About Stephan A. Grupp, MD, PhD
As an attending physician in the Cancer Center, Section Chief of the Cellular Therapy and Transplant Section, Director of the Kelly Center for Cancer Immunotherapy, and the Medical Director of the Cell and Gene Therapy Laboratory, I take on many roles here at CHOP. But in each of them, I’m a pediatric oncologist working to improve outcomes for children battling difficult cancers. I received an M.D. and Ph.D. from the University of Cincinnati College of Medicine and completed residency and fellowship at Harvard Medical School, Boston Children’s Hospital, Dana Farber Cancer Institute and Brigham and Women’s Hospital, before coming to CHOP in 1996.
T cells have the potential to kill cancer cells, but in patients with cancer, they’re not doing that job. By genetically modifying them, we can make the cells behave differently so they’ll attack cancer cells, using genetic engineering with a targeting protein called a chimeric antigen receptor (CAR). Working with our colleagues at the University of Pennsylvania and later with Novartis, we have developed CAR T therapy for children with ALL, opening up a brand new field of medicine and resulting in the first global approval of an engineered cell therapy and also the first gene therapy approved in the US. During the development of this product, I was honored to run the initial CHOP phase 1 trial, the first US multicenter trial of a CAR T therapy, the first international trial (sponsored by Novartis), and the first CAR T pivotal trial. This work has now been extended to using these genetically modified CAR T cells to treat patients with other B cell cancers such as B cell non-Hodgkin lymphoma (NHL), the adult disease chronic lymphocytic leukemia, and other B cell malignancies. In addition to FDA and global health authority approvals, this work has received international attention, generating dozens of high impact scientific publications, including three in the New England Journal of Medicine.
Exciting trials just opening or in the immediate CHOP cell therapy pipeline will extend these results to AML, new forms of ALL, and (coming soon) pediatric solid tumors, providing options for patients with no other therapies available.
Using similar approaches, and working with our colleagues in the Division of Hematology and the CuRED program, we now have multiple clinical trials testing ways to genetically modify bone marrow stem cells to cure diseases like sickle cell anemia and thalassemia. Over 100,000 patients in the US suffer from these red blood cell disorders. This illustrates the commitment of the CTTS to cure patients with cell therapy that have life-threatening, but non-cancer, diseases. Two products for these blood disorders should be FDA-approved in 2023. Over the past 20 years, our Transplant group has evolved to the point where half the transplants we do are for non-cancer diagnoses.
In one of my clinical roles, I also work with patients with the most aggressive form of neuroblastoma, a difficult-to-treat childhood cancer that begins in the peripheral (non-brain) nerve tissue of infants and young children, alongside a world-class team of physicians and multi-disciplinary specialists who are dedicated to treating this disease. The tandem transplant approach that is now standard of care across the country was developed by our transplant group here at CHOP. We also were part of the group that did the nationwide clinical trial establishing antibody-based immunotherapy as the new standard of care in neuroblastoma.
In the lab and the hospital, I am a lab scientist, a cell therapist, and a stem cell transplanter. In the Cell and Gene Therapy Laboratory, we collect cells for transplant and CAR T therapy and manage cell processing: both collecting the original cells and engineering the cells so the right cell type gets into the patient. Recently, we have begun manufacturing CAR T cells for our patients here at CHOP.
What first brought me to CHOP was the opportunity to conduct transplant and leukemia research, and work in CHOP’s intensely translational environment. Today, I run a lab where the research is devoted to developing cell-based and molecularly-targeted therapies to treat leukemia and solid tumors. The goal of all the work I do is to improve treatment options for children with cancer, not just at CHOP but throughout the world. Whether that’s accomplished by offering alternative therapies that are less toxic than today’s standards of care, advanced treatments for high-risk disease that fight cancer in new and different ways, or cures for genetic disorders like sickle cell, if we impact the standard of care, I consider that a success.
Titles
Chief, Cellular Therapy and Transplant Section
Novotny Professor of Pediatrics, Perelman School of Medicine at the University of Pennsylvania
Certifications
Pediatric Hematology-Oncology – American Board of Pediatrics
Pediatrics – American Board of Pediatrics
Awards and Honors
2022, Philadelphia Magazine's Top Doctors in Pediatric Hematology-Oncology
2019, Daniel Drake Medal, University of Cincinnati College of Medicine
2019, Elected to the National Academy of Medicine (NAM)
2018, William Osler Patient Oriented Research Award, Penn Medicine
2016, Scientist of the Year, Philly Geek Awards, Technical.ly
2015, Fred Saunders Lectureship and Award, Canadian Blood and Marrow Transplant Society
2015, Oski Lectureship and Award, American Society of Pediatric Hematology/Oncology
2014, Audrey Evans Service Award, Ronald McDonald House Charities
2014, van Bekkum Prize, European Bone Marrow Transplantation Society
2014, Clinical Research Forum Herbert Pardes First Place Achievement Award
2014, Clinical Research Forum Top 10 Clinical Research US Achievement Award
2014, Pennsylvania Bio Patient Impact Award
2013, Chai Lifeline Community Service Award
2012, Yetta Deitch Novotny Chair, CHOP
2011-2014, Elected to the ASPHO Board of Trustees
2010, Elected to American Pediatric Society
2009, Transplantation Visiting Professor, Hospital for Sick Children and University of Toronto, Toronto, Canada
2008, W.E. Hathaway Visiting Professor, University of Colorado, Denver, CO
2008, Aflac Visiting Professor, Emory University and Children’s Healthcare of Atlanta, Atlanta, GA
2007, Eagles Fly for Leukemia 2007 Lifetime Achievement Award
2003, Elected to the Society for Pediatric Research
2002, Research Recognition Award, Leukemia and Lymphoma Society, Philadelphia, Pennsylvania
2000-2005, Stanford Young Investigator in Molecular Oncology
1997, 1997 Research Award, 5th International Meeting on Blood Cell Transplantation, Omaha, Nebraska
1993-1996, 1993-96 Amy C. Potter Fellow
1987, Bogen Award for Outstanding Medical Student Research, University of Cincinnati College of Medicine
1986, Research Award, Midwest Medical Research Forum, University of Michigan
1981, Graduated Magna cum Laude - University of Cincinnati, Cincinnati, OH
Research Interests
Engineered T cell and stem cell therapies CAR T manufacturing Novel leukemia therapy CAR T Development Core Children's Hospital of Philadelphia Research Institute summary
Education & training
Graduate Degree
PhD - University of Cincinnati College of Medicine PhD, Cincinnati, OH
Medical Degree
MD - University of Cincinnati College of Medicine MD, Cincinnati, OH
Internship
Pediatrics - Children's Hospital, Boston, MA
Residency
Pediatrics - Children's Hospital, Boston, MA
Fellowship
Pediatrics - Harvard Medical School, Boston, MA
Pediatric Hematology/Oncology - Dana Farber Cancer Institute and Children's Hospital, Boston, MA
Research Fellow in Immunology - Brigham and Women's Hospital, Boston, MA
Publications
Publications
2020
Singh N, Lee YG, Shestova O, Ravikumar P, Hayer KE, Hong SJ, Lu XM, Pajarillo R, Agarwal S, Kuramitsu S, Orlando EJ, Mueller KT, Good CR, Berger SL, Shalem O, Weitzman MD, Frey NV, Maude SL, Grupp SA, June CH, Gill S, Ruella M. 2020. Impaired Death Receptor Signaling in Leukemia Causes Antigen-Independent Resistance by Inducing CAR T-cell Dysfunction. Cancer Discovery 10(4):552-567. April 2020. PMID: 32001516.
Kadauke, S, RM Myers, Y Li, R Aplenc, D Baniewicz, DM Barrett, AB Leahy, C Callahan, JG Dolan, JC Fitzgerald, W Gladney, SF Lacey, H Liu, SL Maude, R McGuire, LS Motley, DT Teachey, G Wertheim, L Wray, AM DiNofia, SA Grupp. 2020. Risk-Adapted Preemptive Tocilizumab to Prevent Severe Cytokine Release Syndrome after CTL019 for Pediatric B-Cell Acute Lymphoblastic Leukemia: A Prospective Clinical Trial. J Clin Oncol, in press.
Maus, MV, S Alexander, MR Bishop, JN Brudno, C Callahan, ML Davila, C Diamonte, J Dietrich, JC Fitzgerald, MJ Frigault, TJ Fry, JL Holter-Chakrabarty, KV Komanduri, DW Lee, FL Locke, SL Maude, PL McCarthy, E Mead, SS Neelapu, TG Neilan, BD Santomasso, EJ Shpall, DT Teachey, CJ Turtle, T Whitehead, SA Grupp. 2020. Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune effector cell-related adverse events. J Immunotherapy Cancer, in press.
2019
Park JR, Kreissman SG, London WB, Naranjo A, Cohn SL, Hogarty MD, Tenney SC, Haas-Kogan D, Shaw PJ, Kraveka JM, Roberts SS, Geiger JD, Doski JJ, Voss SD, Maris JM, Grupp SA, Diller L. 2019. Effect of tandem autologous stem cell transplant vs single transplant on event-free survival in patients with high-risk neuroblastoma: A randomized clinical trial. JAMA 322 (8): 746-755. August 27, 2019. PMID: 31454045. PMCID: PMC6714031.
Laetsch TW, Myers GD, Baruchel A, Dietz AC, Pulsipher MA, Bittencourt H, Buechner J, De Moerloose B, Davis KL, Nemecek E, Driscoll T, Mechinaud F, Boissel N, Rives S, Bader P, Peters C, Sabnis HS, Grupp SA, Yanik GA, Hiramatsu H, Stefanski HE, Rasouliyan L, Yi L, Shah S, Zhang J, Harris AC. 2019. Patient-reported quality of life after tisagenlecleucel infusion in children and young adults with relapsed or refractory B-cell acute lymphoblastic leukaemia: a global, single-arm, phase 2 trial. Lancet Oncol. 20 (12): 1710-1718. December 2019. PMID: 31606419.
2018
Maude, SL, TW Laetsch, J Buechner, S Rives, M Boyer, H Bittencourt, P Bader, MR Verneris, HE Stefanski, GD Myers, M Qayed, B De Moerloose, H Hiramatsu, K Schlis, KL Davis, PL Martin, ER Nemecek, GA Yanik, C Peters, A Baruchel, N Boissel, F Mechinaud, A Balduzzi, J Krueger, CH June, BL Levine, P Wood, T Taran, M Leung, KT Mueller, Y Zhang, K Sen, D Lebwohl, MA Pulsipher, and SA Grupp. 2018. Tisagenlecleucel in Children and Young Adults with B Lymphoblastic Leukemia. New England Journal of Medicine. 378(5):439-448. PMID: 29385370.
Teachey DT, Bishop MR, Maloney DG, Grupp SA. 2018. Toxicity management after chimeric antigen receptor T cell therapy: one size does not fit 'ALL'. Nature Reviews Clinical Oncology. April. 15(4):218. PMID: 29434335.
Ruella, M, J Xu, DM Barrett, JA Fraietta, TJ Reich, DE Ambrose, M Klichinsky, O Shestova, PR Patel, I Kulikovskaya, F Nazimuddin, VG Bhoj, EJ Orlando, TJ Fry, H Bitter, SL Maude, BL Levine, CL Nobles, FD Bushman, RM Young, J Scholler, SI Gill, CH June, SA Grupp, SF Lacey and JJ Melenhorst. October 2018. Induction of resistance to chimeric antigen receptor T cell therapy by transduction of a single leukemic B cell. **Nature Medicine 24(10): 1499-1503. PMID 30275568.
*Orlando EJ, Han X, Tribouley C, Wood PA, Leary RJ, Riester M, Levine JE, Qayed M, Grupp SA, Boyer M, De Moerloose B, Nemecek ER, Bittencourt H, Hiramatsu H, Buechner J, Davies SM, Verneris MR, Nguyen K, Brogdon JL, Bitter H, Morrissey M, Pierog P, Pantano S, Engelman JA, Winckler W. October 2018. Genetic mechanisms of target antigen loss in CAR19 therapy of acute lymphoblastic leukemia.
**Nature Medicine 24(10): 1504-1506. PMID 30275569.
**same issue
Lee DW, Santomasso BD, Locke FL, Ghobadi A, Turtle CJ, Brudno JN, Maus MV, Park JH, Mead E, Pavletic S, Go WY, Eldjerou L, Gardner RA, Frey N, Curran KJ, Peggs K, Pasquini M, DiPersio JF, van den Brink MRM, Komanduri KV, Grupp SA, Neelapu SS. 2018. ASBMT Consensus Grading for Cytokine Release Syndrome and Neurological Toxicity Associated with Immune Effector Cells. Biol Blood Marrow Transplant 25(4): 625-638. PMID 30592986.
2017
Bagatell R, Grupp SA. Refining megatherapy, improving outcome in neuroblastoma. Lancet Oncol. 2017 Apr;18(4):423-424. PMID: 28259607.
Bride, KL, T Vincent, K Smith-Whitley, MP Lambert, JJ. Bleesing, AE Seif, CS Manno, J Casper, SA Grupp, and DT Teachey. 2016. Sirolimus is effective in relapsed/refractory autoimmune cytopenias: results of a prospective multi-institutional trial. Blood. 127:17-28. PMID: 26504182, PMCID: PMC4705607.
*Blood Plenary Paper
Singh, N, J Perazzelli, SA Grupp, DM Barrett. 2016. Early memory phenotypes drive T cell proliferation in patients with pediatric malignancies. Sci. Transl. Med. 8, 320ra3. PMID: 26738796.
Teachey, DT, SF Lacey, PA Shaw, JJ Melenhorst, SL Maude, NV Frey, E Pequignot, VE Gonzalez, F Chen, J Finklestein, DM Barrett, SL Weiss, JC Fitzgerald, RA Berg, R Aplenc, C Callahan, SR Rheingold, Z Zheng, S Rose-John, JC White, F Nazimuddin, G Wertheim, BL Levine, CH June, DL Porter, and SA Grupp. 2016. Identification of Predictive Biomarkers for Cytokine Release Syndrome after Chimeric Antigen Receptor T cell Therapy for Acute Lymphoblastic Leukemia. Cancer Discovery 6(6):664-79. PMID: 27076371. PMCID: PMC5448406.
2016
Ruella M, Barrett DM, Kenderian SS, Shestova O, Hofmann TJ, Perazzelli J, Klichinsky M, Aikawa V, Nazimuddin F, Kozlowski M, Scholler J, Lacey SF, Melenhorst JJ, Morrissette JJ, Christian DA, Hunter CA, Kalos M, Porter DL, June CH, Grupp SA, Gill S. Dual CD19 and CD123 targeting prevents antigen-loss relapses after CD19-directed immunotherapies. J Clin Invest. 2016 Oct 3;126(10):3814-3826. PMID: 27571406; PMCID: PMC5096828.
Porter, DL, WT Hwang, NV Frey, SF Lacey, PA Shaw, AW Loren, A Bagg, KT Marcucci, A Shen, V Gonzalez, D Ambrose, SA Grupp, A Chew, Z Zheng, MC Milone, BL Levine, JJ Melenhorst, CH June. 2015. Chimeric Antigen Receptor T Cells Persist and Induce Sustained Remissions in Relapsed Refractory Chronic Lymphocytic Leukemia. Science Translational Medicine. 7:303ra139. PMID: 26333935.
Singh N, Kulikovskaya I, Barrett DM, Binder-Scholl G, Jakobsen B, Martinez D, Pawel B, June CH, Kalos MD, Grupp SA. 2015. T cells targeting NY-ESO-1 demonstrate efficacy against disseminated neuroblastoma. Oncoimmunology. 5(1):e1040216. PMID: 26942053 PMCID: PMC4760344.
2015
Sotillo, E, DM Barrett, KL Black, A Bagashev, D Oldridge, G Wu, R Sussman, C Lanauze, M Ruella, MR Gazzara, NM Martinez, CT Harrington, EY Chung, J Perazzelli, TJ Hofmann, SL Maude, P Raman, A Barrera, S Gill, SF Lacey, JJ Melenhorst, D Allman, E Jacoby, T Fry, C Mackall, Y Barash, KW Lynch, JM Maris, SA Grupp, and A Thomas-Tikhonenko. 2015. Convergence of acquired mutations and alternative splicing of CD19 enables resistance to CART-19 immunotherapy. Cancer Discovery 5(12):1282-95. PMID: 26516065, PMCID: PMC4670800.
2014
Maude SL, Frey N, Shaw PA, Aplenc R, Barrett DM, Bunin NJ, Chew A, Gonzalez VE, Zheng Z, Lacey SF, Mahnke YD, Melenhorst JJ, Rheingold SR, Shen A, Teachey DT, Levine BL, June CH, Porter DL, Grupp SA. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014 Oct 16;371(16):1507-17. PMID: 25317870; PMCID: PMC4267531.
2013
Grupp, SA, M Kalos, D Barrett, R Aplenc, DL Porter, SR Rheingold, DT Teachey, BL Levine, and CH June. 2013. Induction of complete remissions of ALL by chimeric antigen receptor-expressing T cells. New England Journal of Medicine. 368(16):1509-18. PMID: 23527958; PMCID: 4058440; NIHMS: 474709.
Kreissman, SG, RC Seeger, KK Matthay, WB London, R Sposto, SA Grupp, DA Haas-Kogan, MP LaQuaglia, AL Yu, L Diller, A Buxton, JR Park, SL Cohn, JM Maris, CP Reynolds, and JG Villablanca. 2013. Prospective, Randomized Trial of Purged versus Non-Purged Peripheral Blood Stem Cell Transplant for High Risk Neuroblastoma. Lancet Oncology, 14(10):999-1008. PMID: 23890779 ; PMCID: 3963485; NIHMS: 540046.
Teachey, DT, SR Rheingold, SL Maude, G Zugmaier, DM Barrett, AE Seif, KE Nichols, EK Suppa, M Kalos, RA Berg, JC Fitzgerald, R Aplenc, L Gore, and SA Grupp. 2013. Cytokine release syndrome after blinatumomab treatment related to abnormal macrophage activation and ameliorated with cytokine-directed therapy. Blood. 121(26):5154-5157. PMID: 23678006. NIHMS: 607684. PMCID: 4123427.