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 2,000 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.
Investigating graft-host tolerance by establishing transient 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.
Develop novel methods for preventing acute GVHD and treating chronic GVHD in animal models based on mechanistic studies.
(Reading, Writing, Speaking)
English: (Fluent, Fluent, Fluent)
French: (Fluent, Fluent, Fluent)
German: (Fluent, Fluent, Fluent)
Radiolabeled Anti-CD45 Antibody with Reduced-Intensity Conditioning and Allogeneic Transplantation for Younger Patients with Advanced Acute Myeloid Leukemia or Myelodysplastic Syndrome.. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.. 2014.
Prognostic factors and outcomes of severe gastrointestinal GVHD after allogeneic hematopoietic cell transplantation.. Bone marrow transplantation.. 2014.
A clinically applicable tolerance protocol to induce tolerance to vascularized composite allografts without the need for persistent donor cell chimerism. Journal of the American College of Surgeons. 217:S92-S92.. 2013.
Ultrasound-targeted microbubble destruction-mediated gene delivery into canine livers.. Molecular therapy : the journal of the American Society of Gene Therapy. 21(9):1687-94.. 2013.
Fludarabine and 2-Gy TBI is Superior to 2 Gy TBI as Conditioning for HLA-Matched Related Hematopoietic Cell Transplantation: A Phase III Randomized Trial.. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.. 2013.
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. 19(6):949-957.. 2013.
Double umbilical cord blood transplantation in patients with hematologic malignancies using a reduced-intensity preparative regimen without antithymocyte globulin.. Bone marrow transplantation. 48(6):782-786.. 2013.
Graft-versus-Host-Disease after Double Cord Blood Transplantation: A New Look at Its Characteristics.. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 19(6):847-8.. 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.
Comparing High and Low Total Body Irradiation Dose Rates for Minimum-Intensity Conditioning of Dogs for Dog Leukocyte Antigen-Identical Bone Marrow Grafts.. 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.