Transplantation of hematopoietic stem cells derived from bone marrow or peripheral blood following chemotherapy or radiation has been used as a treatment for high-risk cancers for four decades. For children with leukemia who relapse or who are at high risk for relapse, blood or marrow transplantation (BMT) from another individual (allogeneic) can result in cure in approximately 50% patients. Although initially performed as a rescue after very high doses of cytotoxic therapy, it is now evident that the donor immune system contributes to the curative potential allogeneic BMT (known as the graft versus tumor reaction). Unfortunately, when this reaction targets normal tissues (graft versus host disease) serious side effects (including mortality) occur. The primary focus of the Blood and Marrow Transplant Section of the Pediatric Oncology Branch is to develop approaches to increase the curative potential and minimize the toxicity associated with BMT. The projects in the laboratory fall into two broad categories:
I. Increasing the specificity of the graft versus tumor reaction. The primary cells in the donor immune system that mediate the graft versus tumor reaction are lymphocytes (T cells and natural killer cells). Ongoing studies in the BMT section are exploring methods to educate these cells the recognize targets that are expressed exclusively or to a greater degree on tumor cells compared to normal tissues as a means of increasing the specificity and potency of the donor immune response against the tumor.
II. Minimizing graft versus host disease. Current standard methods to prevent graft versus host disease (GVHD) involve the administration of immune suppressive agents. While these can be effective, they can also increase the risk infection and relapse. Dendritic cells are specialized cells responsible for orchestrating immune responses and have been shown to play an important role in the development of GVHD. We have identified that selectively targeting cytokine pathways (Interferon gamma) in donor-derived antigen presenting cells can prevent GVHD. Importantly, in these transplants, the function of lymphocytes appears to remain intact potentially preserving the opportunity to generate immune responses against infections or cancer. Ongoing work is assessing how these principles might be translated into clinical trial.
Terry J. Fry received a B.A. from Colgate University in 1988 and M.D. from Georgetown University in 1992. After completing 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. In 1997, during the research component of his fellowship training, he began working in the laboratory of Dr. Crystal Mackall first as a visiting fellow and subsequently as a post-doctoral fellow. He then became a Staff Clinician in the Pediatric Oncology Branch in 2004. In 2007, Dr. Fry became Chief of the Division of Blood and Marrow Transplantation at Children's National Medical Center, a position he held until 2010 when he returned to the Pediatric Oncology Branch as an Investigator. 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. He also serves as Chair of the Oncology Strategy Group in the Pediatric Blood and Marrow Transplant Consortium and is a member of the Stem Cell Transplantation Committee in Children's Oncology Group.