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)
Alpha Imaging Confirmed Efficient Targeting of CD45-Positive Cells after Astatine-211 (211At)-Radioimmunotherapy for Hematopoietic Cell Transplantation.. Journal of nuclear medicine : official publication, Society of Nuclear Medicine.. 2015.
Reevaluation of the pretransplant assessment of mortality score after allogeneic hematopoietic transplantation.. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 21(5):848-54.. 2015.
Anti-CD28 Antibody-Initiated Cytokine Storm in Canines.. Transplantation direct. 1(2). 2015.
In Support of a Patient-Driven Initiative and Petition to Lower the High Price of Cancer Drugs.. Mayo Clinic proceedings.. 2015.
Long-term outcomes of patients with persistent indolent B cell malignancies undergoing nonmyeloablative allogeneic transplantation.. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 21(2):281-7.. 2015.
Design and Validation of an Augmented Hematopoietic Cell Transplantation-Comorbidity Index Comprising Pretransplant Ferritin, Albumin, and Platelet Count for Prediction of Outcomes after Allogeneic Transplantation.. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.. 2015.
Pre-transplant comorbidity burden and post-transplant chronic graft-versus-host disease.. British journal of haematology. 171(3):411-416.. 2015.
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. 20(9). 2014.
Prognostic factors and outcomes of severe gastrointestinal GVHD after allogeneic hematopoietic cell transplantation.. Bone marrow transplantation.. 2014.
Achieving Tolerance in a Mismatched VCA Transplant While Reducing The Risk of GVHD: Goal of Transient Chimerism.. Transplantation. 98:409-410.. 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.