Terry J. Fry, M.D.
Pediatric Oncology Branch
Building 10 - Hatfield CRC, Room 2-3942
Bethesda, MD 20892-1104
Despite substantial improvements in outcome over the past three decades, leukemia remains a leading cause of cancer-related mortality in children. Furthermore, even in patients cured by modern risk-adapted therapy, there are substantial long-term sequelae. Thus, newer treatments are needed, particularly those not based on standard cytotoxic agents. The Hematologic Malignancies Section (HMS) conducts lab-based translational research focused on immunotherapeutic approaches for leukemia. Clinical efforts in the treatment of leukemia occur within the Pediatric Oncology Branch (POB) clinical program where early phase clinical trials are conducted. The work currently taking place in the HMS and in the POB clinical program is focused on the use of cell-based immunotherapy for pediatric leukemia as well as more basic studies in leukemia biology. In particular, the HMS is now heavily focused on the use of genetically modified T cells expressing chimeric antigen receptors (CAR) for the treatment of pediatric hematologic malignancies.
Aim 1: Translational development of chimeric antigen receptors for the treatment of pediatric leukemia
Using in vitro studies and xenograft models of pediatric acute lymphoblastic leukemia (ALL) in immune-deficient mice, the HMS performed preclinical optimization of a novel CD22-targeted CAR. Dr. Fry leads the first-in-human clinical trial using this CAR in children and young adults with relapsed and refractory pre-B cell ALL. The HMS also has other CAR constructs that target antigens expressed on pre-B cell ALL that will enter clinical trials in the near future. Finally, the HMS is extending CAR therapy to other forms of pediatric leukemia, including acute myelogenous leukemia (AML) and T cell ALL.
Aim 2: Elucidation of the biologic principles involved in the immunotherapeutic targeting of pediatric leukemia
The HMS utilizes a novel syngeneic murine model of CAR therapy for pre-B cell ALL that is being used to study in vivo biology of CAR therapy in an immunologically intact system. Collectively, these studies have provided an opportunity to study immunotherapeutic resistance of ALL to CAR T cells.
Terry J. Fry received a B.A. from Colgate University in 1988 and an M.D. from Georgetown University in 1992. After completing a pediatric residency at Georgetown in 1995, he served as Chief Pediatric Resident. From 1996-1999, Dr. Fry undertook fellowship training in pediatric hematology and oncology at Johns Hopkins University. After postdoctoral training in the laboratory of Dr. Crystal Mackall, Dr. Fry established a research program focused on the immunology of stem cell transplantation as a platform for cancer immunotherapy. Dr. Fry became Chief of the Division of Blood and Marrow Transplantation at Children's National Medical Center in 2007, a position he held until 2010 when he returned to the Pediatric Oncology Branch as Head of the Hematologic Malignancies Section. He is a member of multiple societies including the American Society of Hematology, the American Association of Immunology and the American Society of Blood and Marrow Transplantation and was elected into the American Society of Clinical Investigation. He also serves in leadership positions in the Oncology Strategy Group in the Pediatric Blood and Marrow Transplant Consortium and the Cellular Therapy Committee in the Children's Oncology Group.
Shand JC, Qin H, Nasholm N, Capitini CM, Fry TJ. Minor antigen distribution predicts site-specific graft-versus-tumor activity of adoptively transferred, minor antigen-specific CD8 T Cells. Biol Blood Marrow Transplant. 2014;20(1):26-36.
Capitini CM, Nasholm NM, Chien CD, Larabee SM, Qin H, Song YK, Klover PJ, Hennighausen L, Khan J, Fry TJ. Absence of STAT1 in donor-derived plasmacytoid dendritic cells results in increased STAT3 and attenuates murine GVHD. Blood. 2014;124(12):1976-86.
Mackall CL, Merchant MS, Fry TJ. Immune-based therapies for childhood cancer. Nat Rev Clin Oncol. 2014;11(12):693-703.
Capitini CM, Nasholm NM, Duncan BB, Guimond M, Fry TJ. Graft-versus-host disease impairs vaccine responses through decreased CD4+ and CD8+ T cell proliferation and increased perforin-mediated CD8+ T cell apoptosis. J Immunol. 2013;190(3):1351-9.
Fry TJ, Mackall CL. T-cell adoptive immunotherapy for acute lymphoblastic leukemia. Hematology Am Soc Hematol Educ Program. 2013;2013:348-53.
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This page was last updated on September 20th, 2017