Rainer F. Storb
M.D., A Ludwig University, 1960.
Transplantation biology; basic and translational research into the biology of allogeneic blood and marrow hematopoietic cell transplantation (HCT)
Our laboratory pursues basic and translational research into the biology of allogeneic blood and marrow cell transplantation (HCT) both in a preclinical model and in human patients with malignant and nonmalignant hematologic diseases. Following are some of our goals:
Developing radically different approaches for HCT that have minimal toxicity, do not ablate the marrow, and thus are safe enough to administer in the ambulatory care setting. We have replaced the conventionally used intense conditioning regimens by optimal postgrafting immunosuppression which was aimed at controlling both serious graft-vs-host disease and host-versus-graft reactions. Studies in a preclinical model showed that conditioning with a nonmyeloablative dose of only 2 Gy total body irradiation followed by a short postgrafting course of the antimetabolite mycophenolate mofetil and the calcineurin inhibitor cyclosporine allowed stable engraftment of allogeneic hematopoietic cells. A further reduction in the TBI dose was accomplished by blocking T cell costimulatory signals while triggering the T cell receptor with donor antigen, resulting in antigen-specific hyporesponsiveness. The nonmyeloablative HCT approach outlined here was translated to the clinic and mixed hematopoietic chimerism was used as a platform for adoptive immunotherapy of malignant and nonmalignant diseases in more than 700 human patients who were not eligible for conventional HCT (such as elderly or medically infirm patients). With this kind of transplant, the eradication of underlying disease is accomplished through graft-versus tumor effects rather than high-dose cytotoxic therapy. Trials using both HLA-matched related and unrelated grafts and graft-vs-tumor effects have shown unanticipated success in both B-cell and myeloid malignancies. The elimination of the last vestiges of pre-transplant radiation through induction of host vs. donor immunological non-responsiveness continues to be a major research goal, which will be particularly important for pediatric patients and those with nonmalignant diseases, e.g. sickle cell disease.
Defining polymorphic minor histocompatibility antigens on solid tumors, e.g. breast, prostate, and colon cancer, and designing strategies to direct alloreactivites to specific tumor targets
This effort, done in collaboration with colleagues from both the Benaroya Research Institute and the University of Washington’s Genome Center, involves whole genome scanning for therapeutic minor histocompatibility antigens involved in allogeneic graft vs. tumor effects.
Investigating graft-host tolerance by establishing mixed hematopoietic chimerism as a prelude for acceptance of solid organ transplants. Kidney, lung, small bowel, and pancreatic islets have been used to test the stringency of tolerance.
Examining the transdifferentiation potential of adult primitive hematopoietic or mesenchymal stem cells which may be used to regenerate epithelial and muscle cells. A pre-clinical model of Duchenne muscular dystrophy is being pursued to test the plasticity of such cells.
Extending the use of nonmarrow-ablative allogeneic hematopoietic cell transplants and cell therapy to include patients with metastic solid tumors and autoimmune diseases.
(Reading, Writing, Speaking)
English: (Fluent, Fluent, Fluent)
French: (Fluent, Fluent, Fluent)
German: (Fluent, Fluent, Fluent)
Donor Lymphocyte Infusion for Relapsed Hematological Malignancies after Allogeneic Hematopoietic Cell Transplantation: Prognostic Relevance of the Initial CD3(+) T Cell Dose.. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.. 2013.
Allogeneic Hematopoietic Cell Transplantation Following Minimal Intensity Conditioning: Predicting Acute Graft-versus-Host Disease and Graft-versus-Tumor Effects.. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.. 2013.
Graft-versus-host disease and graft-versus-tumor effects after allogeneic hematopoietic cell transplantation.. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 31(12):1530-8.. 2013.
Mapping contrast agent uptake and retention in MRI studies of myocardial perfusion: case control study of dogs with Duchenne muscular dystrophy.. The international journal of cardiovascular imaging.. 2012.
Edward Donnall Thomas (1920-2012).. Nature. 491(7424):334.. 2012.
Association between Calcineurin Inhibitor Blood Concentrations and Outcomes after Allogeneic Hematopoietic Cell Transplantation.. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 18(3):414-422.. 2012.
Successful Regional Delivery and Long-term Expression of a Dystrophin Gene in Canine Muscular Dystrophy: A Preclinical Model for Human Therapies.. Molecular therapy : the journal of the American Society of Gene Therapy.. 2012.
Mesenchymal stromal cells: a new tool against graft-versus-host disease? Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 18(6):822-40.. 2012.
Autologous hematopoietic cell transplantation following high-dose immunosuppressive therapy for advanced multiple sclerosis: long-term results.. Bone marrow transplantation. 47(7):946-951.. 2012.
Success of allogeneic marrow transplantation for children with severe aplastic anaemia.. British journal of haematology. 158(1):120-8.. 2012.
Allo-SCT for multiple myeloma: a review of outcomes at a single transplant center.. Bone marrow transplantation.. 2012.
Activation of Notch Signaling During ex vivo Expansion Maintains Donor Muscle Cell Engraftment.. Stem cells (Dayton, Ohio).. 2012.
Prevention of graft-vs.-host disease.. Expert opinion on pharmacotherapy. 13(12):1737-50.. 2012.
Analyzing Cellular Immunity to AAV in a Canine Model Using ELISPOT Assay.. Methods in molecular biology (Clifton, N.J.). 792:65-74.. 2012.
Decreased Serum Albumin as a Biomarker for Severe Acute Graft-vs-Host Disease after Reduced-Intensity Allogeneic Hematopoietic Cell Transplantation.. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 17(11):1594-1601.. 2011.