Stephan A. Grupp, MD, PhD

Stephan A. Grupp, MD, PhD

Stephan A. Grupp, MD, PhD, is Director of the Cancer Immunotherapy Program, Director of Translational Research for the Center for Childhood Cancer Research at CHOP and Medical Director of the Stem Cell Laboratory. 

Areas of Expertise: Development of engineered T cell therapies such as CTL019, Novel leukemia therapy, Stem cell transplants, Treatment of high-risk neuroblastoma
Locations: Main Campus
Appointments and Referrals: 1-800-TRY-CHOP (1-800-879-2467)

Background

As an attending physician in the Cancer Center, Director of the Cancer Immunotherapy Program, Director of Translational Research of the Center for Childhood Cancer Research, and the Director of the Stem Cell Laboratory, I take on many roles here at CHOP. But in each of them, I’m a pediatric oncologist working to improve outcomes for children battling difficult cancers. I trained at Harvard, at Boston Children’s and the Dana Farber Cancer Institute, and came to CHOP in 1996.

Working with our colleagues at the University of Pennsylvania, we have recently opened a phase I clinical trial called CART19 or CTL019. We’re using genetically modified T cells in this trial to treat patients with B cell cancers such as ALL, B cell non-Hodgkin lymphoma (NHL), the adult disease chronic lymphocytic leukemia and other B cell malignancies. T cells have the potential to kill cancer cells, but in patients with cancer, they’re not doing their job. By modifying them, we can make the cells behave differently so they’ll attack cancer cells, using an engineered targeting protein called a chimeric antigen receptor (CAR). Initial results show that this could be an effective therapy for patients with B cell cancers. Indeed, our initial results show some of the most powerful activity against cancer of any clinical trial testing engineered cell therapy to date. This has received international attention, and some of this work has been published recently in Science Translational Medicine and twice in the New England Journal of Medicine.

In one of my clinical roles, I also work with patients with the most aggressive form of neuroblastoma, a difficult-to-treat childhood cancer that begins in the peripheral (non-brain) nerve tissue of infants and young children. I work alongside a world-class team of physicians and multi-disciplinary specialists who are dedicated to treating this disease. The neuroblastoma team at CHOP does studies of the patient’s genetics and the unique characteristics of their disease to offer a personalized treatment approach. We were part of the group that did the nationwide clinical trial establishing antibody-based immunotherapy as the new standard of care in neuroblastoma.

Outside of the clinic, in the lab and the hospital, I am a lab scientist and stem cell transplanter. In the Stem Cell Laboratory we manage cell processing, both collecting the original cells and engineering the cells to the right cell type gets into the patient. My work in the lab has intersected with my clinical work several times. Working with a group of four institutions, we pioneered a treatment called tandem transplant — two sequential courses of high-dose chemotherapy with stem cell transplant given six weeks apart. This clinical trial was open for about 10 years and helped raise the bar for treating high-risk neuroblastoma. The tandem treatment protocol achieved three-year survival rates of almost 60 percent, three times the survival rate before stem cell transplants, and still the best phase 2 treatment result in the world literature. This tandem transplant approach has also now been tested in a nationwide phase 3 trial, which was also successful and has established tandem transplantation as the U.S. standard of care.

Similarly, we developed a new class of drugs for acute lymphocytic leukemia (ALL, the most common childhood cancer), based on a target in the ALL cell called mTOR. We have shown that drugs which target mTOR have activity against ALL, and we have taken this treatment to another nationwide phase 3 randomized trial.

What first brought me to CHOP was the opportunity to conduct transplant and leukemia research, and work in CHOP’s intensely translational environment. Today, I run a lab where the research is devoted to developing cell-based and molecularly-targeted therapies to treat leukemia and solid tumors.

 The goal of all the work I do is to improve treatment options for children with cancer, not just at CHOP but across the U.S. Whether that’s accomplished by offering alternative therapies that are less toxic than today’s standards of care, or advanced treatments for high-risk disease that fight cancer in new and different ways, if we impact the standard of care, I consider that a success.

Education and Training

Medical School

MD - University of Cincinnati College of Medicine MD, Cincinnati, OH

Internship

Pediatrics - Children's Hospital, Boston, MA

Residency

Pediatrics - Children's Hospital Fellowships

Fellowship

Pediatrics - Harvard Medical School, Boston, MA
Pediatric Hematology/Oncology - Dana Farber Cancer Institute and Children's Hospital, Boston, MA
Research Fellow in Immunology - Brigham and Women's Hospital, Boston, MA

Board Certification

Pediatric Hematology-Oncology
Pediatrics

Graduate Degree

PhD - University of Cincinnati College of Medicine PhD, Cincinnati, OH

Titles and Academic Titles

Chief, Cellular Therapy and Transplant Section

Director, Cancer Immunotherapy Program

Director of Translational Research, Center for Childhood Cancer Research at The Children's Hospital of Philadelphia

Attending Physician, Division of Oncology

Medical Director, Stem Cell Laboratory

Deputy Chair, IACUC

Yetta Deitch Novotny Endowed Chair in Pediatric Oncology

Novotny Professor of Pediatrics, Perelman School of Medicine at the University of Pennsylvania

Departments and Services

Research Interests

B lymphocyte receptor signaling in leukemia
Developmental lymphopoiesis
Children's Hospital of Philadelphia Research Institute summary

Publications

Papers

2016

Bride KL, Vincent T, Smith-Whitley K, Lambert MP, Bleesing JJ, Seif AE, Manno CS, Casper J, Grupp SA, Teachey DT. Sirolimus is effective in relapsed/refractory autoimmune cytopenias: results of a prospective multi-institutional trial. Blood. 2016 Jan 7;127(1):17-28

2015

Porter, DL, WT Hwang, NV Frey, SF Lacey, PA Shaw, AW Loren, A Bagg, KT Marcucci, A Shen, V Gonzalez, D Ambrose, SA Grupp, A Chew, Z Zheng, MC Milone, BL Levine, JJ Melenhorst, CH June. 2015. Chimeric Antigen Receptor T Cells Persist and Induce Sustained Remissions in Relapsed Refractory Chronic Lymphocytic Leukemia. Science Translational Medicine. In press.

Haiying, Q, M Cho, W Haso, L Zhang, S Tasian, H Zarni Oo, G Neri, Y Lin, J Zhou, B Mallon, S Maude, D Teachey, D Barrrett, R Orentas, M Daugaard, P Sorensen, SA Grupp, and T Fry. 2015. Eradication of pre B cell ALL using chimeric antigen receptor-expressing T cells targeting the TSLPR oncoprotein. Blood. In press.

Pulsipher, MA, C Carlson, B Langholz, DA Wall, KR Schultz, N Bunin, I Kirsch, JM Gastier-Foster, M Borowitz, C Desmarais, D Williamson, M Kalos, and SA Grupp. 2015. IgH-V(D)J NGS-MRD measurement pre- and early post-allotransplant defines very low- and very high-risk ALL patients. Blood, in press. DOI 10.1182/blood-2014-12-615757.

Pulsipher, MA, B Langholz, DA Wall, KR Schultz, N Bunin, W Carroll, E Raetz, S Gardner, RK Goyal, J Gastier-Foster, M Borowitz, D Teachey, and SA Grupp. 2015. Risk factors and timing of relapse after allogeneic transplantation in pediatric ALL: for whom and when should interventions be tested? Bone Marrow Transplantation. In press. doi:10.1038/bmt.2015.103

Maude, SL, DT Teachey, DL Porter, and SA Grupp. 2015. CD19-targeted Chimeric Antigen Receptor T cell Therapy for Acute Lymphoblastic Leukemia. Blood, in press.

Maude, SL, S Dolai, C Delgado-Martin, TL Vincent, A Robbins, A Selvanathan, T Ryan, J Hall, AC Wood, SK Tasian, SP Hunger, ML Loh, CG Mullighan, BL Wood, ML Hermiston, SA Grupp, RB Lock, and DT Teachey. 2015. Efficacy of JAK/STAT pathway inhibition in murine xenograft models of early T-cell precursor (ETP) acute lymphoblastic leukemia. Blood, in press.

2014

Grupp, SA. 2014. Advances in T-cell therapy for ALL. Best Practice & Research Clinical Haematology, doi:10.1016/j.beha.2014.10.014

Yanik, GA, SA Grupp, MA Pulsipher, JE Levine, KR Schultz, DA Wall, B Langholz, CC Dvorak, K Alangaden, RK Goyal, ES White, JM Collura, MA Skeens, S Eid, EM Pierce, and KR Cooke. 2014. TNF receptor inhibitor therapy for the treatment of children with idiopathic pneumonia syndrome (IPS). A joint Pediatric Blood and Marrow Transplant Consortium (PBMTC) and Children’s Oncology Group (COG) study (ASCT0521). Biol. Blood and Marrow Trans. In press.  PMID: 25270958.

Lee, DW, R Gardner, DL Porter, CU Louis, N Ahmed, M Jensen, SA Grupp, and CL Mackall, C. L. 2014, Current concepts in the diagnosis and management of cytokine release syndrome. Blood 124(2): 188-195. PMID: 24876563.

Lankester, AC, F Locatelli, P Bader, E Rettinger, M Egeler, S Katewa, MA Pulsipher, S Nierkens, K Schultz, R Handgretinger, SA Grupp, JJ Boelens, and CM Bollard. 2014. Will post transplant cell therapies for pediatric patients become standard of care? Biol Blood Marrow Transplant. DOI: 10.1016/j.bbmt.2014.07.018; S1083-8791(14)0044-3. PMID: 25064748.

June, CH, MV Maus, G Plesa, LA Johnson, Y Zhao, BL Levine, SA Grupp, and DL Porter. 2014. Engineered T cells for cancer therapy. Cancer Immunol Immunother., DOI: 10.1007/s00262-014-1568-1. Sep673(9):969-75.  Epub 2014 June 19. PMID: 24943274

Cutler, C,  B Logan, B, R. Nakamura, L Johnston, S Choi, D. Porter, WJ Hogan, M Pasquini, ML MacMillan, J Hsu, EK Waller, SA Grupp, P McCarthy, J Wu, ZH Hu, SL Carter, MM Horowitz, JH Antin. 2014. Tacrolimus/sirolimus versus tacrolimus/methotrexate as GVHD prophylaxis after matched, related donor allogeneic hematopoietic cell transplantation. Blood. 8 Aug. 21; 124(8):1372-7. Doi: 10.1182/blood-2014-04-567164, Epub 2014 June 30. PMID: 24982504.

Singh, NA, X Liu, J Hulitt, S Jiang, CH June, SA Grupp, DM Barrett, and Y Zhao. 2014. Nature of tumor control by permanently and transiently-modified GD2 chimeric antigen receptor T cells in xenograft models of neuroblastoma. Cancer Immunology Research. DOI: 10.1158/2326-6066.CIR-14-0051.

Maude, SL N Frey, PA Shaw, R Aplenc, DM Barrett, NJ Bunin, A Chew, VE Gonzalez, Z Zheng, SF Lacey, BL Levine, YD Mahnke, JJ Melenhorst, SR Rheingold, A Shen, DT Teachey, CH June, DL Porter, and SA Grupp. 2014. Sustained Remissions with Chimeric Antigen Receptor T Cells For Leukemia. New England Journal of Medicine, 371:1507-17.  PMID: 25317870.  NIHMSID: 640298.

Pulsipher, MA, B Langholz, DA Wall, KR Schultz, N Bunin, W Carroll, E Raetz, S Gardner, RK Goyal, J Gastier-Foster, M Borowitz, DT Teachey, and SA Grupp. 2014. The Role of Acute Graft versus Host Disease and Minimal Residual Disease in Predicting Risk of Relapse after Allogeneic Transplantation for Childhood ALL:  Subanalysis of a Phase III Trial COG ASCT0431/PBMTC ONC051. Blood, in press. PMID: 24497539; PMCID: 3968388.

Pulsipher, MA, B Langholz, DA Wall, KR Schultz, N Bunin, WL Carroll, E Raetz, S Gardner, JM Gastier-Foster, D Howrie, RK Goyal, JG Douglas, M Borowitz, Y Barnes, DT Teachey, C Taylor, SA Grupp. 2014. The addition of sirolimus to tacrolimus/methotrexate GVHD prophylaxis in children with ALL: A phase 3 Children’s Oncology Group/Pediatric Blood and Marrow Transplant Consortium trial. Blood, Blood 123(13): 2017-2025.

Bassiri, H, R Das, P Guan, DM Barrett, PJ Brennan, PP Banerjee, SJ Wiener, JS Orange, MB Brenner, SA Grupp, KE Nichols. 2014. iNKT cell cytotoxic responses control T-lymphoma growth in vitro and in vivo. Cancer Immunol Res, Jan 1; 2(1):59-69, doi: 10.11578/2326-6066.CIR-13-0104. PMID: 24563871; PMCID: 3927984; NIHMS: 542978.

Gill, S, SK Tasian, M Ruella, O Shestova, Y Li, DL Porter, M Carroll, G Danet-Desnoyers, J Scholler, SA Grupp, CH June, and M Kalos. 2014. Efficacy against human acute myeloid leukemia and myeloablation of normal hematopoiesis in a mouse model using chimeric antigen receptor-modified T cells. Blood. Published ahead of print March 4, 2014, doi:10.1182/blood-2013-09-529537. PMID: 24596416; PMCID: 3983612.

Maude, SL, DM Barrett, DT Teachey, and SA Grupp. 2014. Managing cytokine release  syndrome associated with novel T cell engaging therapies. Cancer J, March/April, 20(2):119-122. Doi.1097/PPO.0000000000000035. PMID: 24667956. NIHMS: 607703. PMCID: 4119809.

Maus, MV, SA Grupp, DL Porter, and CH June. 2014. Antibody-modified T cells: CARs take the front seat for hematologic malignancies. Blood. Epub ahead of print. PMID: 24578504; PMCID: 3999751.

Barrett, DM, N Singh, DL Porter, SA Grupp and CH June. 2014. Chimeric antigen receptor therapy for cancer. Ann Rev Med. Jan 14;65:333-47. Doi: 10.1146/annurev-med-060512-150254. Epub 2013 Nov 20. PMID: 24274181.  NIHMS: 607694. PMCID: 4120077.

Barrett, DM, N Singh, X Liu, S Jiang, CH June, SA Grupp and Y Zhao. 2014. Relation of clinical culture method to T-cell memory status and efficacy in xenograft models of adoptive immunotherapy.  Cytotherapy. Jan 15. pii:S1465-3249(13)00759. Doi:10.1016/j.jcyt.2013.10.013. [Epub ahead of print]  PMID: 24439255; PMCID: 3988256; NIHMS: 559247.

Barrett, DM, DT Teachey, and SA Grupp. 2014. Toxicity Management for Patients Receiving Novel T-cell Engaging Therapies. Current Opinion on Pediatrics. Feb, 26(1):43-9. Doi: 10.1097/MOP.0000000000000043.  PMID: 24362408. NIHMS: 607686. PMCID: 4198063.

2013

Teachey, DT, SR Rheingold, SL Maude, G Zugmaier, DM Barrett, AE Seif, KE Nichols, EK Suppa, M Kalos, RA Berg, JC Fitzgerald, R Aplenc, L Gore, and SA Grupp. 2013. Cytokine release syndrome after blinatumomab treatment related to abnormal macrophage activation and ameliorated with cytokine-directed therapy. Blood. 121(26):5154-5157. Doi: 10.1182/blood-2013-02-485623. Epub 2013 May 15. PMID: 23678006. NIHMS: 607684.  PMCID: 4123427.

Barrett, DM, X Liu, S Jiang, CH June, SA Grupp*, and Y Zhao*. 2013. Regimen specific effects of RNA-modified chimeric antigen receptor T cells in mice with advanced leukemia. Human Gene Therapy, 24(8):717-27. Doi: 10.1089/hum.2013.075.  PMID: 23883116.  PMCID: 374289.
*equal contribution

Schultz, RK, KS Baker, JJ Boelens, CM Bollard, RM Egeler, M Cowan, R Ladenstein, A. Lankester, F Locatelli, A Lawitschka, JE Levine, M Loh, E Nemecek, C Niemeyer, VK Prasad, V Rocha, S Shenoy, B Strahm, P Veys, D wall, P Bader, SA Grupp, MA Pulsipher, and C Peters. 2013. Challenges and opportunities for international cooperative studies in pediatric hematopoietic cell transplantation priorities of the Westhafen Intercontinental Group. Biol Blood Marrow Transplant, Sep. 19(9):1279-87. Doi: 10.1016/j.bbmt.2013.07.006. Epub 2013 Jul 21. PMID: 23883618. NIHMS: 607798. PMCID: 4198148.

Kreissman, SG, RC Seeger, KK Matthay, WB London, R Sposto, SA Grupp, DA Haas-Kogan, MP LaQuaglia, AL Yu, L Diller, A Buxton, JR Park, SL Cohn, JM Maris, CP Reynolds, and JG Villablanca. 2013. Prospective, Randomized Trial of Purged versus Non-Purged Peripheral Blood Stem Cell Transplant for High Risk Neuroblastoma. Lancet Oncology, 14(10):999-1008.  PMID: 23890779 ; PMCID: 3963485; NIHMS: 540046.

Grupp, SA, M Kalos, D Barrett, R Aplenc, DL Porter, SR Rheingold, DT Teachey, BL Levine, and CH June. 2013. Induction of complete remissions of ALL by chimeric antigen receptor-expressing T cells. New England Journal of Medicine. 368(16):1509-18. PMID: 23527958;  PMCID: 4058440; NIHMS: 474709.

Posters and Presentations

2014

Grupp, SA, SL Maude, P Shaw, R Aplenc, DM Barrett, C Callahan, A Chew, SF Lacey, BL Levine JJ Melenhorst, L Motley, SR Rheingold, A Shen, DT Teachey, PA Wood, DL Porter and CH June.  T cells engineered with a chimeric antigen receptor targeting CD19 (CTL019 cells) produce significant in vivo proliferation, complete responses and long-term persistence without GVHD in children and adults with relapsed, refractory ALL. 56th Annual American Society of Hematology, December 6-9, 2014, San Francisco, CA.  Blood, Abstract #380.

*Platform presentation by Dr. Grupp

*Featured in ASH Press Program

*Featured in Best of ASH

Grupp, SA, N Frey, R Aplenc, B Levine, S Maude, S Rheingold, C. Strait Barker, D Teachey, Y Mahnke, D Porter, C June. T cells engineered with a chimeric antigen receptor (CAR) targeting CD19 (CTL019 cells) produce significant in vivo proliferation, complete responses and long-term persistence without GVHD in children and adults with relapsed, refractory ALL. 40th European Bone Marrow Transplant Meeting, April 2014, Milan, Italy, Abstract #1.

* Winner, van Bekkum Prize

1st Plenary Abstract Presentation

Frey, NV, BL Levine, SF Lacey, SA Grupp, SL Mude, SJ Schuster, P Shaw, W-T Hwang, MA Wasik, A Obstfeld, M Leung, A Shen, SG Ericson, JJ Melenhorst, CH June and DL Porter.  Refractory cytokine release syndrome in recipients of chimeric antigen receptor (CAR) T cells.  56th Annual American Society of Hematology, December 6-9, 2014, San Francisco, CA.  Blood, Abstract #2296.

V Bhoj, MC Milone, CH June, DL Porter, SA Grupp, JJ Melenhorst, SF Lacey, C Callahan,  J Capobianchi, G Wertheim and Y Mahnke.  Humoral immunity and plasma cell changes in patients responding to CD19-specific chimeric antigen receptor (CAR)-modified T-cell adoptive immunotherapy.  56th Annual American Society of Hematology, December 6-9, 2014, San Francisco, CA.  Blood, Abstract #1110.

Ruella, M, D Barrett, SS Kenderian, O Shestova, TJ Hofmann, J Scholler, SF Lacey, JJ Melenhorst, F Nazimuddin, M Kalos, DL Porter, CH June, SA Grupp, and SI Gill.  Novel chimeric antigen receptor T cells for the treatment of CD19-negative relapses occurring after CD19-targeted immunotherapies. 56th Annual American Society of Hematology, December 6-9, 2014, San Francisco, CA.  Blood, Abstract #966.

Porter, DL, SF Lacey, W-T Hwang, P Shaw, NV Frey, SL Maude, JJ Melenhorst, M Lichtman, DT Teachey, A Shen, A Quintas-Cardamas, PA Wood, BL Levine, CH June and SA Grupp.  Cytokine release syndrome (CRS) after chimeric antigen receptor (CAR) T cell therapy for relapsed/refractory (R/R) CLL.  56th Annual American Society of Hematology, December 6-9, 2014, San Francisco, CA.  Blood, Abstract #1983.

2013

Grupp, SA, NV Frey, R Aplenc, DM Barrett, A Chew, M Kalos, BL Levine, M Lichtman, SL Maude, SR Rheingold, A Shen, C Strait, DT Teachey, PA Wood, D Porter and CH June.  T cells engineered with a chimeric antigen receptor (CAR) targeting CD19 (CTL019) produce significant in vivo proliferation, complete responses and long-term persistence without Gvhd in children and adults with relapsed, refractory ALL. 55th Annual American Society of Hematology, December 7-10, 2013, New Orleans, LA. Blood, Abstract #614.

*Platform presentation by Dr. Grupp

*Featured in ASH Press Program

Gill, S, SK Tasian, M Ruella, O Shestova, Y Li, DL Porter, M Carroll, G Danet-Desnoyers, J Scholler, SA Grupp, CH June and M Kalos. Anti-CD123 chimeric antigen receptor T cells (CART-123) provide a novel myeloablative conditioning regimen that eradicates human acute myeloid leukemia in preclinical models. 55th Annual American Society of Hematology, December 7-10, 2013, New Orleans, LA. Blood, Abstract #703.

Pulsifer, MA, CS Carlson, K Mark, DA Wall, KR Schultz, N Bunin, M Kalos, D Cindy, D Williamson, j Gastier-Foster, MJ Borowitz and SA Grupp.  Striking predictive power for relapse and decreased survival associated with detectable minimal residual disease by IGH VDJ deep sequencing of bone marrow pre- and post- allogeneic transplant in children with B-lineage ALL: A subanalysis of the COG ASCT0431/PBMTC ONC051 study. 55th Annual American Society of Hematology, December 7-10, 2013, New Orleans, LA. Blood, Abstract #731.

Qin, H, M Cho, W Haso, L Zhang, DM Barrett, RJ Orentas, SA Grupp and TJ Fry.  Pre-clinical development of a novel chimerical antigen receptor targeting high-risk pediatric ALL over-expressing Tslpr. 55th Annual American Society of Hematology, December 7-10, 2013, New Orleans, LA. Blood, Abstract #614.

Awards and Honors

2018, William Osler Patient Oriented Research Award, Penn Medicine

2015, Fred Saunders Lectureship and Award, Canadian Blood and Marrow Transplant Society

2015, Oski Lectureship and Award, American Society of Pediatric Hematology/Oncology

2014, Audrey Evans Service Award, Ronald McDonald House Charities

2014, van Bekkum Prize, European Bone Marrow Transplantation Society

2014, Clinical Research Forum Herbert Pardes First Place Achievement Award

2014, Clinical Research Forum Top 10 Clinical Research US Achievement Award

2014, Pennsylvania Bio Patient Impact Award

2013, Visiting Professor, Stanford University, Stanford, CA

2013, Chai Lifeline Community Service Award

2012, Yetta Deitch Novotny Chair, CHOP

2011-2014, Elected to the ASPHO Board of Trustees

2010, Elected to American Pediatric Society

2009, Transplantation Visiting Professor, Hospital for Sick Children and University of Toronto, Toronto, Canada

2008, W.E. Hathaway Visiting Professor, University of Colorado, Denver, CO

2008, Aflac Visiting Professor, Emory University and Children’s Healthcare of Atlanta, Atlanta, GA

2007, Eagles Fly for Leukemia 2007 Lifetime Achievement Award

2003, Elected to the Society for Pediatric Research

2002, Research Recognition Award, Leukemia and Lymphoma Society, Philadelphia, Pennsylvania

2000-2005, Stanford Young Investigator in Molecular Oncology

1997, 1997 Research Award, 5th International Meeting on Blood Cell Transplantation, Omaha, Nebraska

1993-1996, 1993-96 Amy C. Potter Fellow

1987, Bogen Award for Outstanding Medical Student Research, University of Cincinnati College of Medicine

1986, Research Award, Midwest Medical Research Forum, University of Michigan

1981, Graduated Magna cum Laude - University of Cincinnati, Cincinnati, OH