Home Our Team Faculty Stephan A. Grupp, MD, PhD Profile

Stephan A. Grupp, MD, PhD

Stephan A. Grupp, MD, PhD

Director of Translational Research

Director of the Pediatric Hematology/Oncology Fellowship Program

Medical Director, Stem Cell Laboratory

Professor of Pediatrics, University of Pennsylvania School of Medicine

Contact Stephan A. Grupp, MD, PhD

Resume

  • Department: Pediatrics
  • Division: Oncology
  • Primary Address:
    Oncology/BMT CTRB 3006
    3501 Civic Center Blvd.
    Philadelphia, PA 19104
  • 215-590-5476

    Expertise

    ITMAT:

    Engineered T cell therapy

    Signal transduction in lymphoid malignancies

    RESEARCH:

    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

    Appointments

    • Professor of Pediatrics, University of Pennsylvania School of Medicine (2012 – present)
    • Associate Professor of Pediatrics, University of Pennsylvania School of Medicine (2006 – 2012)
    • Assistant Professor of Pediatrics, University of Pennsylvania School of Medicine (1996 – 2006)

    Education

    • M.D., University of Cincinnati College of Medicine (1987)
    • Ph.D., University of Cincinnati College of Medicine (1985)
    • B.S., University of Cincinnati (Magna cum laude) (1981)

    Extended Bio

    As an attending physician in the Cancer Center, the 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.

    In one of my clinical roles, I specialize in 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 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. I’m also the chair of the Stem Cell Transplant Discipline and transplant clinical trial development for the nationwide Children’s Oncology Group (COG). My work in the lab has intersected with my clinical work several times. Working with a group of four institutions, I 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 is now being tested in a nationwide phase 3 trial to prove whether it should become the national 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 molecularly-targeted therapies and cell-based therapies to treat leukemia and solid tumors.

    Working with our colleagues at the University of Pennsylvania, we have recently opened a phase I clinical trial called CART19. 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.

    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.

    Publications

    • Barrett David M, Liu Xiaojun, Jiang Shuguang, June Carl H, Grupp Stephan A, Zhao Yangbing. Regimen-Specific Effects of RNA-Modified Chimeric Antigen Receptor T Cells in Mice with Advanced Leukemia. Human gene therapy. Vol 24(8) . 2013 Aug:717-27.
    • Hale G A, Arora M, Ahn K W, He W, Camitta B, Bishop M R, Bitan M, Cairo M S, Chan K, Childs R W, Copelan E, Davies S M, Perez M A D, Doyle J J, Gale R P, Vicent M G, Horn B N, Hussein A A, Jodele S, Kamani N R, Kasow K A, Kletzel M, Lazarus H M, Lewis V A, Myers K C, Olsson R, Pulsipher M, Qayed M, Sanders J E, Shaw P J, Soni S, Stiff P J, Stadtmauer E A, Ueno N T, Wall D A, Grupp S A. Allogeneic hematopoietic cell transplantation for neuroblastoma: the CIBMTR experience. Bone Marrow Transplantation. Vol 48(8) . 2013 Aug:1056-64.
    • Kreissman Susan G, Seeger Robert C, Matthay Katherine K, London Wendy B, Sposto Richard, Grupp Stephan A, Haas-Kogan Daphne A, Laquaglia Michael P, Yu Alice L, Diller Lisa, Buxton Allen, Park Julie R, Cohn Susan L, Maris John M, Reynolds C Patrick, Villablanca Judith G. Purged versus non-purged peripheral blood stem-cell transplantation for high-risk neuroblastoma (COG A3973): a randomised phase 3 trial. The Lancet Oncology. 2013 Jul.
    • Seif A E, Naranjo A, Baker D L, Bunin N J, Kletzel M, Kretschmar C S, Maris J M, McGrady P W, von Allmen D, Cohn S L, London W B, Park J R, Diller L R, Grupp S A. A pilot study of tandem high-dose chemotherapy with stem cell rescue as consolidation for high-risk neuroblastoma: Children's Oncology Group study ANBL00P1. Bone marrow transplantation. Vol 48(7) . 2013 Jul:947-52.
    • Schultz Kirk R, Baker K Scott, Boelens Jaap J, Bollard Catherine M, Egeler R Maarten, Cowan Mort, Ladenstein Ruth, Lankester Arjan, Locatelli Franco, Lawitschka Anita, Levine John E, Loh Mignon, Nemecek Eneida, Niemeyer Charlotte, Prasad Vinod K, Rocha Vanderson, Shenoy Shalini, Strahm Brigitte, Veys Paul, Wall Donna, Bader Peter, Grupp Stephan A, Pulsipher Michael A, Peters Christina. Challenges and Opportunities for International Cooperative Studies in Pediatric Hematopoeitic Cell Transplantation: Priorities of the Westhafen Intercontinental Group. Biology of blood and marrow transplantation. 2013 Jul.
    • Teachey David T, Rheingold Susan R, Maude Shannon L, Zugmaier Gerhard, Barrett David M, Seif Alix E, Nichols Kim E, Suppa Erica K, Kalos Michael, Berg Robert A, Fitzgerald Julie C, Aplenc Richard, Gore Lia, Grupp Stephan A. Cytokine release syndrome after blinatumomab treatment related to abnormal macrophage activation and ameliorated with cytokine-directed therapy. Blood. Vol 121(26) . 2013 Jun:5154-7.
    • Grupp Stephan A, Dvorak Christopher C, Nieder Michael L, Levine John E, Wall Donna A, Langholz Bryan, Pulsipher Michael A. Children's Oncology Group's 2013 blueprint for research: stem cell transplantation. Pediatric Blood & Cancer. Vol 60(6) . 2013 Jun:1044-7.
    • Grupp Stephan A, Kalos Michael, Barrett David, Aplenc Richard, Porter David L, Rheingold Susan R, Teachey David T, Chew Anne, Hauck Bernd, Wright J Fraser, Milone Michael C, Levine Bruce L, June Carl H. Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. The New England Journal of Medicine. Vol 368(16) . 2013 Apr:1509-18.
    • Goyal Rakesh K, Han Kelong, Wall Donna A, Pulsipher Michael A, Bunin Nancy, Grupp Stephan A, Mada Sripal R, Venkataramanan Raman. Sirolimus pharmacokinetics in early postmyeloablative pediatric blood and marrow transplantation. Biology of Blood and Marrow Transplantation. Vol 19(4) . 2013 Apr:569-75.
    • Goyal, RK, K Han, DA Wall, MA Pulsipher, N Bunin, SA Grupp, SR Mada, and R Venkataramanan.. Sirolimus pharmacokinetics in early post myeloablative pediatric blood and marrow transplantation.. Biology of Blood and Marrow Transplantation. 2012 Dec.