Stephan A. Grupp, MD, PhD

faculty photo
Professor of Pediatrics
Department: Pediatrics
Graduate Group Affiliations

Contact information
The Children's Hospital of Philadelphia
Colket Translational Research Building, Room 3006
3501 Civic Center Boulevard
Philadelphia, PA 19104
Office: 215-590-5475
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

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.: 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, Dec 2019.

Chong EA, Levine BL, Grupp SA, Davis MM, Siegel DL, Maude SL, Gladney WL, Frey NV, Porter DL, Hwang WT, Chong ER, June CH, Schuster SJ.: CAR T cell viability release testing and clinical outcomes: is there a lower limit? Blood 134(21): 1873-1875, Nov 2019.

Bader P, Salzmann-Manrique E, Balduzzi A, Dalle JH, Woolfrey AE, Bar M, Verneris MR, Borowitz MJ, Shah NN, Gossai N, Shaw PJ, Chen AR, Schultz KR, Kreyenberg H, Di Maio L, Cazzaniga G, Eckert C, van der Velden VHJ, Sutton R, Lankester A, Peters C, Klingebiel TE, Willasch AM, Grupp SA, Pulsipher MA.: More precisely defining risk peri-HCT in pediatric ALL: pre- vs post-MRD measures, serial positivity, and risk modeling. Blood Adv. 3(21): 3393-3405, Nov 2019.

Pillai V, Muralidharan K, Meng W, Bagashev A, Oldridge DA, Rosenthal J, Van Arnam J, Melenhorst JJ, Mohan D, DiNofia AM, Luo M, Cherian S, Fromm JR, Wertheim G, Thomas-Tikhonenko A, Paessler M, June CH, Luning Prak ET, Bhoj VG, Grupp SA, Maude SL, Rheingold SR.: CAR T-cell therapy is effective for CD19-dim B-lymphoblastic leukemia but is impacted by prior blinatumomab therapy. Blood Adv. 3(22): 3539-3549, Nov 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.: 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, Aug 2019.

Esiashvili N, Lu X, Ulin K, Laurie F, Kessel S, Kalapurakal JA, Merchant TE, Followill DS, Sathiaseelan V, Schmitter MK, Devidas M, Chen Y, Wall DA, Brown PA, Hunger SP, Grupp SA, Pulsipher MA.: Higher Reported Lung Dose Received during Total Body Irradiation for Allogeneic Hematopoietic Stem Cell Transplantation in Children with Acute Lymphoblastic Leukemia is Associated with Inferior Survival: A Report from the Children's Oncology Group. Int J Radiat Oncol Biol Phys 104(3): 513-521, Jul 2019.

Hill-Kayser CE, Tochner Z, Li Y, Kurtz G, Lustig RA, James P, Balamuth N, Womer R, Mattei P, Grupp S, Mosse YP, Maris JM, Bagatell R.: Outcomes after Proton Therapy for Treatment of Pediatric High-Risk Neuroblastoma. Int J Radiat Oncol Biol Phys. 104(2), Jun 2019.

Stein AM, Grupp SA, Levine JE, Laetsch TW, Pulsipher MA, Boyer MW, August KJ, Levine BL, Tomassian L, Shah S, Leung M, Huang PH, Awasthi R, Mueller KT, Wood PA, June CH.: Tisagenlecleucel Model-Based Cellular Kinetic Analysis of Chimeric Antigen Receptor-T Cells. CPT Pharmacometrics Syst Pharmacol. 8(5): 285-295, May 2019.

Rajat K. Das, Lauren Vernau, Stephan A. Grupp and David M. Barrett: Naive T cell deficits at diagnosis and after chemotherapy impair cell therapy potential in pediatric cancers. Cancer Discovery 9(4): 492-499, Apr 2019.

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.: ASBMT Consensus Grading for Cytokine Release Syndrome and Neurological Toxicity Associated with Immune Effector Cells. Biol Blood Marrow Transplant. 25(4): 625-638, Apr 2019.

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Last updated: 12/09/2019
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