Stephan A. Grupp, MD, PhD

faculty photo
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.
Permanent link
 
> Perelman School of Medicine   > Faculty   > Details

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

Kernan NA, Richardson PG, Smith AR, Triplett BM, Antin JH, Lehmann L, Messinger Y, Liang W, Hume R, Tappe W, Soiffer RJ, Grupp SA: Defibrotide for the treatment of hepatic veno-occlusive disease/sinusoidal obstruction syndrome following nontransplant-associated chemotherapy: Final results from a post hoc analysis of data from an expanded-access program. Pediatr Blood Cancer 65(10): e27269, October 2018.

Leahy AB, Elgarten CW, Grupp SA, Maude SL, Teachey DT.: Tisagenlecleucel for the treatment of B-cell acute lymphoblastic leukemia. Expert Rev Anticancer Ther. 18(10): 959-971, October 2018.

Laetsch TW, Maude SL, Milone MC, Davis KL, Krueger J, Cardenas AM, Eldjerou LK, Keir CH, Wood PA, Grupp SA: False-positive results following lentiviral-based tisagenlecleucel therapy with select HIV-1 NAT methods. Blood April 2018 Notes: doi: 10.1182/blood-2017-12-822940. [Epub ahead of print]

Teachey DT, Bishop MR, Maloney DG, Grupp SA.: Toxicity management after chimeric antigen receptor T cell therapy: one size does not fit 'ALL'. Nature Reviews Clinical Oncology 15(4): 218, April 2018.

Bride, KL, TL Vincent, SY Im, R Aplenc, DM Barrett, WL Carroll, R Carson, Y Dai, M Devidas, KP Dunsmore, T Fuller, T Glisovic-Aplenc, TM Horton, SP Hunger, ML Loh, SL Maude, EA Raetz, SS Winter, SA Grupp, ML Hermiston, BL Wood, and DT Teachey: Preclinical efficacy of daratumumab in T-cell acute lymphoblastic leukemia. Blood 131(9): 995-999, March 2018.

Dvorak CC, Satwani P, Stieglitz E, Cairo MS, Dang H, Pei Q, Gao Y, Wall D, Mazor T, Olshen AB, Parker JS, Kahwash S, Hirsch B, Raimondi S, Patel N, Skeens M, Cooper T, Mehta PA, Grupp SA, Loh ML.: Disease burden and conditioning regimens in ASCT1221, a randomized phase II trial in children with juvenile myelomonocytic leukemia: A Children's Oncology Group study. Pediatr Blood Cancer. March 2018 Notes: [Epub ahead of print]

Prabhu VV, Talekar MK, Lulla AR, Kline CLB, Zhou L, Hall J, Van den Heuvel APJ, Dicker DT, Babar J, Grupp SA, Garnett MJ, McDermott U, Benes CH, Pu JJ, Claxton DF, Khan N, Oster W, Allen JE, El-Deiry WS.: Single agent and synergistic combinatorial efficacy of first-in-class small molecule imipridone ONC201 in hematological malignancies. Cell Cycle 19: 1-11, February 2018.

Mashegu H, Smith L, Li Y, Seif A, Stephan A. Grupp, Nancy J. Bunin.: The role of peritoneal drainage in veno-occlusive disease in pediatric patients post hematopoietic stem cell transplant. Bone Marrow Transplantation Journal. February 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.: Tisagenlecleucel in Children and Young Adults with B Lymphoblastic Leukemia. New England Journal of Medicine 378(5): 439-448, February 2018.

Richman SA, Nunez-Cruz S, Moghimi B, Li LZ, Gershenson ZT, Mourelatos Z, Barrett DM, Grupp SA, Milone MC: High-Affinity GD2-Specific CAR T Cells Induce Fatal Encephalitis in a Preclinical Neuroblastoma Model. Cancer Immunol Res. 6(1): 36-46, January 2018.

back to top
Last updated: 09/14/2018
The Trustees of the University of Pennsylvania