Stephan A. Grupp

faculty photo
Professor of Pediatrics
Attending Physician, The Children's Hospital of Philadelphia, University of Pennsylvania
Deputy Chair, IACUC, Children's Hospital of Philadelphia, University of Pennsylvania
Director of Translational Research, Center for Childhood Cancer Research, The Children's Hospital of Philadelphia, University of Pennsylvania
Department: Pediatrics

Contact information
Oncology/BMT CTRB 3006
3501 Civic Center Blvd.
Philadelphia, PA 19104
Office: 215-590-5476
Fax: (215) 590-3770
Graduate Group Affiliations
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.
Permanent link
 

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.

Description of Itmat Expertise

Engineered T cell therapy

Signal transduction in lymphoid malignancies

Selected Publications

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 23(6): 997-1004, June 2017.

Richardson PG, Smith AR, Triplett BM, Kernan NA, Grupp SA, Antin JH, Lehmann L, Shore T, Iacobelli M, Miloslavsky M, Hume R, Hannah AL, Nejadnik B, Soiffer RJ6; Defibrotide Study Group.: Defibrotide for Patients with Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome: Interim Results from a Treatment IND Study. Biol Blood Marrow Transplant. 23(6): 997-1004, June 2017 Notes: Epub 2017 Mar 8.

Singh N, Hofmann TJ, Gershenson Z, Levine BL,Stephan A. Grupp, Teachey DT, Barrett DM: Monocyte lineage-derived IL-6 does not affect chimeric antigen receptor T-cell function. Cytotherapy May 2017 Notes: doi: 10.1016/j.jcyt.2017.04.001. [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 129(17): 2395-2407, April 2017.

Rochelle Bagatell, Stephan A Grupp: Refining megatherapy, improving outcome in neuroblastoma. The Lancet Oncology 18(4): 423-424, April 2017.

Richardson PG, Smith AR, Triplett BM, Kernan NA, Grupp SA, Antin JH, Lehmann L, Miloslavsky M, Hume R, Hannah AL, Nejadnik B, Soiffer RJ.: Earlier defibrotide initiation post-diagnosis of veno-occlusive disease/sinusoidal obstruction syndrome improves Day +100 survival following haematopoietic stem cell transplantation. Br J Haematol. April 2017 Notes: [Epub ahead of print]

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 45(2): e124-e131, February 2017.

Yu H, Sotillo E, Harrington C, Wertheim G, Paessler M, Maude SL, Rheingold SR, Grupp SA, Thomas-Tikhonenko A, Pillai V.: Repeated loss of target surface antigen after immunotherapy in primary mediastinal large B cell lymphoma. Am J Hematol. 92(1): E11-E13, January 2017 Notes: Epub 2016 Nov 21.

Tasian SK, Teachey DT, Li Y, Shen F, Harvey RC, Chen IM, Ryan T, Vincent TL, Willman CL, Perl AE, Hunger SP, Loh ML, Carroll M, Grupp SA.: Potent efficacy of combined PI3K/mTOR and JAK or ABL inhibition in murine xenograft models of Ph-like acute lymphoblastic leukemia. Blood 129(2): 177-187, January 2017 Notes: Epub 2016 Oct 24.

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

back to top
Last updated: 07/25/2017
The Trustees of the University of Pennsylvania