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Stephan A. Grupp, MD, PhD

Stephan A. Grupp, MD, PhD

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Professor of Pediatrics
Department: Pediatrics
Graduate Group Affiliations

Contact information
Oncology/BMT CTRB 3006
3501 Civic Center Blvd.
Philadelphia, PA 19104
Office: 215-590-5476
Fax: (215) 590-3770
Education:
B.S.
University of Cincinnati (Magna cum laude), 1981.
Ph.D.
University of Cincinnati College of Medicine, 1985.
M.D.
University of Cincinnati College of Medicine, 1987.
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Description of Research Expertise

Research Interests

Role of the B cell receptor complex in B cell signaling and lymphoid development

Research Summary

Basic Science. The primary focus of my lab’s work is the development of targeted cell therapies and study of molecular signaling pathways in ALL. Our group has leveraged studies using primary human ALL xenografts into treatments being tested in a number of clinical trials.

We have demonstrated the importance of the mTOR pathway in leukemia and lymphoma, and demonstrated that inhibitors of mTOR signal transduction (such as sirolimus) are effective agents against pre-B ALL and against the lymphoproliferative disorder ALPS. These findings have direct translational significance in both ALL and ALPS, leading to Phase I, II, III (ASCT0431) and pilot trials in these diseases. We also demonstrated that signaling through the IL-7 receptor is key in the response of early B ALL cells to mTOR inhibitors. IL-7 and a related molecule called TSLP reverse the effect of mTOR inhibitors on pre-B ALL cells, providing insights into the potential mechanisms of the mTOR effect and a further opportunity for signal transduction inhibition in ALL. We are the ALL Xenograft Core Lab for the COG.


Translational. As the CCCR Director of Translational Research, I oversee research into clinical use of hematopoietic stem cells and T cell-based therapies. As an example, we have performed trials to improve outcome in neuroblastoma (NBL), a disease that has <15% long-term survival with chemo and ~35% with single autologous stem cell transplant (SCT). This has also lead to a phase III trial (ANBL0532) in the COG.

More recently, our group has been working with Dr. Carl June and the Penn Translational Research Program on chimeric antigen receptor (CAR)-based engineered T cell therapies. One target is CD19 in ALL, where we have developed chimeric immunoreceptor-armed T cells in an ongoing basic and translational collaboration with the June group. This approach has now been taken into pilot trials at CHOP and Penn. The first three adult patients on this clinical trial experienced remarkable clinical responses and unprecedented persistence and expansion of the therapeutic cells. We are now seeing similar results in pediatric patients with ALL.

Selected Publications

Rochelle Bagatell, Stephan A Grupp: Refining megatherapy, improving outcome in neuroblastoma. The Lancet Oncology March 1 2017 Notes: Epub ahead of print.

Sarah K Tasian, Saad S Kenderian, Feng Shen, Marco Ruella, Olga Shestova, Miroslaw Kozlowski, Yong Li, April Schrank-Hacker, Jennifer JD Morrissette, Martin Carroll, Carl H June, Stephan A Grupp, and Saar Gill: Optimized Depletion of Chimeric Antigen Receptor T-Cells in Murine Xenograft Models of Human Acute Myeloid Leukemia. Blood February 2017 Notes: Epub ahead of print.

Paul G. Richardson, MD; Angela R. Smith, MD, MS; Brandon M. Triplett, MD; Nancy A. Kernan, MD; Stephan A. Grupp, MD, PhD; Joseph H. Antin, MD; Leslie Lehmann, MD; Tsiporah Shore, MD; Massimo Iacobelli, MD; Maja Miloslavsky, PhD; Robin Hume, MS; Alison L. Hannah, MD; Bijan Nejadnik, MD; Robert J. Soiffer, MD; and the Defibrotide Study Group: Defibrotide for Patients with Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome (VOD/SOS): Interim Results from a Treatment IND Study. Biology of Blood and Marrow Transplantation 2017 Notes: In press.

Bride K. L. Vincent T. Smith-Whitley K. Lambert M. P. Bleesing J. J. Seif A. E. Teachey D. T.: Sirolimus is effective in relapsed refractory autoimmune cytopenias: results of a prospective multi-institutional Blood 127 : 17–28, Jan 2016

M Fidanza, A E Seif, A DeMicco, N Rolf, S Jo, B Yin, Y Li, D M Barrett, J Duque-Afonso, M L Cleary, C H Bassing, S A Grupp and G S D Reid: Inhibition of precursor B-cell malignancy progression by toll-like receptor ligand-induced immune responses. Leukemia leu.2016.152(10), Jun 2016 Notes: DOI:10.1038/leu.2016.152.

132. Richardson PG, Riches ML, Kernan NA, Brochstein JA, Mineishi S, Termuhlen AM, Arai S, Grupp SA, Guinan EC, Martin PL, Steinbach G, Krishnan A, Nemecek ER, Giralt S, Rodriguez T, Duerst R, Doyle J, Antin JH, Smith A, Lehmann L, Champlin R, Gillio A, Bajwa R, D'Agostino RB Sr, Massaro J, Warren D, Miloslavsky M, Hume RL, Iacobelli M, Nejadnik B, Hannah AL, Soiffer RJ.: Phase 3 trial of defibrotide for the treatment of severe veno-occlusive disease and multi-organ failure. Blood 127(13): 1656-65, March 31 2016.

Singh, N, J Perazzelli, SA Grupp, DM Barrett: Early memory phenotypes drive T cell proliferation in patients with pediatric malignancies. Science Translational Medicine 8(320), January 6 2016.

Liu X, Barrett D M, Jiang S, Fang C, Kalos M, Grupp S A, June C H, Zhao Y: Improved anti-leukemia activities of adoptively transferred T cells expressing bispecific T-cell engager in mice. Blood cancer journal 6(6): e430, 2016.

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: Identification of Predictive Biomarkers for Cytokine Release Syndrome after Chimeric Antigen Receptor T cell Therapy for Acute Lymphoblastic Leukemia. Cancer Discovery 2016.

Fitzgerald, JC, SL Weiss, SL Maude, DM Barrett, SF Lacey, JJ Melenhorst, P Shaw, RA Berg, CH June, DL Porter, NV Frey, SA Grupp, and DT Teachey: Cytokine Release Syndrome After Chimeric Antigen Receptor T Cell Therapy for Acute Lymphoblastic Leukemia. Critical Care Medicine 2016.

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Last updated: 05/19/2017
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