Daniel H. Fowler, MD
Year elected: 2007
Current membership category: Senior
Principal InvestigatorNIH/National Cancer Institutes
Building 10, Room 12N226
9000 Rockville Pike
Bethesda, MD 20892
United States of America
My laboratory focuses on donor Th2 cells for modulation of graft rejection, graft-versus-host disease (GVHD), and graft-versus-tumor (GVT) effects. To generate Th2 cells ex vivo, donor CD4 cells are co-stimulated in the presence of IL-4 and IL-2; most recently, we have found that ex vivo expansion in rapamycin generates anti-apoptotic Th2 cells (Th2.rapa cells) that have increased in vivo survival and increased capacity to modulate allogeneic responses. In murine models, we found that Th2 cell allograft augmentation represents a novel approach to reduce GVHD while partially preserving a GVT effect. In murine models of fully-MHC disparate graft rejection, we found that Th2 cell allograft augmentation represents a new approach to enhance alloengraftment across genetic barriers. We have completed a first generation clinical trial that has demonstrated the safety and feasibility of Th2 cell allograft augmentation for therapy of refractory hematologic malignancy. Currently, we are testing rapamycin-generated Th2 cells in a pilot clinical at the NCI. In this trial, we have identified that Th2.rapa cells appear to promote alloengraftment, thereby permitting prompt donor chimerism after out-patient chemotherapy. Ongoing murine efforts seek to identify mechanisms of Th2 cell action, whereas clinical efforts will expand to include transplantation across increased genetic disparity.
National Institutes of Health (Primary)
Darryl C. Zeldin, MD is the representative at this institution.