Stephan A. Grupp

faculty photo
Professor of Pediatrics
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

Grupp Stephan A: Advances in T-cell therapy for ALL. Best practice & research. Clinical haematology 27(3-4): 222-228, December 2014.

Singh Nathan, Liu Xiaojun, Hulitt Jessica, Jiang Shuguang, June Carl H, Grupp Stephan A, Barrett David M, Zhao Yangbing: Nature of Tumor Control by Permanently and Transiently Modified GD2 Chimeric Antigen Receptor T Cells in Xenograft Models of Neuroblastoma. Cancer immunology research 2(11): 1059-70, Nov 2014.

Maude Shannon L, Frey Noelle, Shaw Pamela A, Aplenc Richard, Barrett David M, Bunin Nancy J, Chew Anne, Gonzalez Vanessa E, Zheng Zhaohui, Lacey Simon F, Mahnke Yolanda D, Melenhorst Jan J, Rheingold Susan R, Shen Angela, Teachey David T, Levine Bruce L, June Carl H, Porter David L, Grupp Stephan A: Chimeric antigen receptor T cells for sustained remissions in leukemia. The New England Journal of Medicine 371(16): 1507-17, Oct 2014.

Yanik Gregory A, Grupp Stephan A, Pulsipher Michael A, Levine John E, Schultz Kirk R, Wall Donna A, Langholz Bryan, Dvorak Christopher C, Alangaden Keith, Goyal Rakesh K, White Eric S, Collura Jennifer M, Skeens Micah A, Eid Saada, Pierce Elizabeth M, Cooke Kenneth R: TNF-Receptor Inhibitor Therapy for the Treatment of Children with Idiopathic Pneumonia Syndrome. A Joint Pediatric Blood and Marrow Transplant Consortium and Children's Oncology Group Study (ASCT0521). Biology of blood and marrow transplantation Sep 2014.

June Carl H, Maus Marcela V, Plesa Gabriela, Johnson Laura A, Zhao Yangbing, Levine Bruce L, Grupp Stephan A, Porter David L: Engineered T cells for cancer therapy. Cancer immunology, immunotherapy : CII 63(9): 969-75, Sep 2014.

Lankester Arjan C, Locatelli Franco, Bader Peter, Rettinger Eva, Egeler Maarten, Katewa Satyendra, Pulsipher Michael A, Nierkens Stefan, Schultz Kirk, Handgretinger Rupert, Grupp Stephan A, Boelens Jaap Jan, Bollard Catherine M: Will Post-Transplantation Cell Therapies for Pediatric Patients Become Standard of Care? Biology of blood and marrow transplantation Jul 2014.

Lee Daniel W, Gardner Rebecca, Porter David L, Louis Chrystal U, Ahmed Nabil, Jensen Michael, Grupp Stephan A, Mackall Crystal L: Current concepts in the diagnosis and management of cytokine release syndrome. Blood 124(2): 188-95, Jul 2014.

Barrett David M, Singh Nathan, Liu Xiaojun, Jiang Shuguang, June Carl H, Grupp Stephan A, Zhao Yangbing: Relation of clinical culture method to T-cell memory status and efficacy in xenograft models of adoptive immunotherapy. Cytotherapy 16(5): 619-30, May 2014.

Gill Saar, Tasian Sarah K, Ruella Marco, Shestova Olga, Li Yong, Porter David L, Carroll Martin, Danet-Desnoyers Gwenn, Scholler John, Grupp Stephan A, June Carl H, Kalos Michael: Preclinical targeting of human acute myeloid leukemia and myeloablation using chimeric antigen receptor-modified T cells. Blood 123(15): 2343-54, Apr 2014.

Maus Marcela V, Grupp Stephan A, Porter David L, June Carl H: Antibody-modified T cells: CARs take the front seat for hematologic malignancies. Blood 123(17): 2625-35, Apr 2014.

back to top
Last updated: 12/12/2014
The Trustees of the University of Pennsylvania