Stephan Grupp | Chief, Cellular Therapy and Transplant Section
The Children's Hospital of Philadelphia

Stephan Grupp, Chief, Cellular Therapy and Transplant Section, The Children's Hospital of Philadelphia

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.

Appearances:



Conference Day 2: Friday 17th May 2019 @ 09:40

Keynote presentation: CAR T Immunotherapy – Opportunities and Challenges

  • Understand the role of CAR-T cell therapy in relapsed ALL
  • Understand the risk factors and therapies for Cytokine Release Syndrome (CRS)
  • Understand the importance of T cell proliferation and persistence in CAR-T cell efficacy

Conference Day 2: Friday 17th May 2019 @ 10:00

Keynote panel: Innovations in cellular and combination immunotherapy: current learnings, challenges and future applications

· Using the immune system to identify and fight cancer cells: where are we and what do we need to maximise patient benefit in the future?· Improving cellular immunotherapy success by using genetic biomarkers to create precision medicines and improve success rates· Where are we with combination immunotherapy, what needs to be done to improve efficiency and effectiveness in the future. · Moving from oncology to non-oncology applications, how can we make the shift to new therapy indications· Preventing relapse and resistance
last published: 18/Mar/19 11:45 GMT

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