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
University of Cincinnati (Magna cum laude), 1981.
University of Cincinnati College of Medicine, 1985.
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

Nathan Singh, Noelle V. Frey, Boris Engels, David M. Barrett, Olga Shestova, Pranali Ravikumar, Katherine D. Cummins, Yong Gu Lee, Raymone Pajarillo, Inkook Chun, Amy Shyu, Steven L. Highfill, Andrew Price, Linlin Zhao, Liaomin Peng, Brian Granda, Melissa Ramones, Xueqing Maggie Lu, David A. Christian, Jessica Perazzelli, Simon F. Lacey, Nathan H. Roy, Janis K. Burkhardt, Florent Colomb, Mohammad Damra, Mohamed Abdel-Mohsen, Ting Liu, Dongfang Liu, Daron M. Standley, Regina M. Young, Jennifer L. Brogdon, Stephan A. Grupp, Carl H. June, Shannon L. Maude, Saar Gill, Marco Ruella: Antigen-independent activation enhances the efficacy of 4-1BB-costimulated CD22 CAR T cells. Nature Medicine Apr 2021 Notes:

Sophia Faude, Jane Wei, Kavitha Muralidharan, Xiaoming Xu, Gerald Wertheim, Michele Paessler, Vijay G Bhoj, Stephan A Grupp, Shannon L Maude, Susan R Rheingold, Vinodh Pillai: Absolute lymphocyte count proliferation kinetics after CAR T-cell infusion impact response and relapse. Blood Advances 5(8): 2128-2136, Apr 2021.

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. : 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 39(8): 920-930, Mar 2021.

Rahul Arya, David M Barrett, Stephan A Grupp, Jan Joseph Melenhorst: Improving and Maintaining Responses in Pediatric B-Cell Acute Lymphoblastic Leukemia Chimeric Antigen Receptor-T Cell Therapy. Cancer 27(2): 151-158, Mar-Apr 2021.

Haydar Frangoul, M.D., David Altshuler, M.D., Ph.D., M. Domenica Cappellini, M.D., Yi-Shan Chen, Ph.D., Jennifer Domm, M.D., Brenda K. Eustace, Ph.D., Juergen Foell, M.D., Josu de la Fuente, M.D., Ph.D., Stephan Grupp, M.D., Ph.D., Rupert Handgretinger, M.D., Tony W. Ho, M.D., Antonis Kattamis, M.D., Andrew Kernytsky, Ph.D., Julie Lekstrom-Himes, M.D., Amanda M. Li, M.D., Franco Locatelli, M.D., Markus Y. Mapara, M.D., Ph.D., Mariane de Montalembert, M.D., Damiano Rondelli, M.D., Akshay Sharma, M.B., B.S., Sujit Sheth, M.D., Sandeep Soni, M.D., Martin H. Steinberg, M.D., Donna Wall, M.D., Angela Yen, Ph.D., and Selim Corbacioglu, M.D.: CRISPR-Cas9 Gene Editing for Sickle Cell Disease and β-Thalassemia. The New England Journal of Medicine 384(3): 252-260, Jan 2021.

Jochen Buechner, Stephan A Grupp, Hidefumi Hiramatsu, David T Teachey, Susana Rives, Theodore W Laetsch, Gregory A Yanik, Patricia Wood, Rakesh Awasthi, Lan Yi, Andrea Chassot-Agostinho, Lamis K Eldjerou, Barbara De Moerloose: Practical guidelines for monitoring and management of coagulopathy following tisagenlecleucel CAR T-cell therapy. Blood Adv. 5(2): 593-601, Jan 2021.

Haneen Shalabi, Juliane Gust, Agne Taraseviciute, Pamela L Wolters, Allison B Leahy, Carlos Sandi, Theodore W Laetsch, Lori Wiener, Rebecca A Gardner, Veronique Nussenblatt, Joshua A Hill, Kevin J Curran, Timothy S Olson, Colleen Annesley, Hao-Wei Wang, Javed Khan, Marcelo C Pasquini, Christine N Duncan, Stephan A Grupp, Michael A Pulsipher, Nirali N Shah: Beyond the storm - subacute toxicities and late effects in children receiving CAR T cells. Nat Rev Clin Oncol Jan 2021 Notes: Epub ahead of print.

Zhiliang Bai, Stefan Lundh, Dongjoo Kim, Steven Woodhouse, David M Barrett, Regina M Myers, Stephan A Grupp, Marcela V Maus, Carl H June, Pablo G Camara, J Joseph Melenhorst, Rong Fan: Single-cell multiomics dissection of basal and antigen-specific activation states of CD19-targeted CAR T cells. J Immunother Cancer 2021 Notes: doi: 10.1136/jitc-2020-002328, epub ahead of print.

Gregory M Chen, Changya Chen, Rajat K Das, Peng Gao, Chia-Hui Chen, Shovik Bandyopadhyay, Yang-Yang Ding, Yasin Uzun, Wenbao Yu, Qin Zhu, Regina M Myers, Stephan A. Grupp, David M Barrett, Kai Tan: Integrative bulk and single-cell profiling of pre-manufacture T-cell populations reveals factors mediating long-term persistence of CAR T-cell therapy. Cancer Discovery 2021 Notes: Epub ahead of print.

Brian D Weiss, Gregory Yanik, Arlene Naranjo, Fan F Zhang, Wendy Fitzgerald, Barry L Shulkin, Marguerite T Parisi, Heidi Russell, Stephan Grupp, Luke Pater, Peter Mattei, Yael Mosse, Hollie A Lai, Jason A Jarzembowski, Hiroyuki Shimada, Judith G Villablanca, Roger Giller, Rochelle Bagatell, Julie R Park, Katherine K Matthay: A safety and feasibility trial of (131) I-MIBG in newly diagnosed high-risk neuroblastoma: A Children's Oncology Group study. Pediatr Blood Cancer 2021 Notes: doi: 10.1002/pbc.29117. Online ahead of print.

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Last updated: 06/22/2021
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