Fas Ligand-Expressing Hematopoietic Cells for Transplantation

Rejection of allografts is mediated by activated T cells that recognize alloantigen presented by dendritic and other antigen presenting cells. To decrease the immune response against allografts, Johns Hopkins University researchers have genetically modified dendritic cells with retroviral vectors to stably express Fas ligand (FasL). Since activated T cells express Fas, contact with FasL should initiate apoptosis. Data demonstrate that FasL was not toxic to the dendritic cells themselves. Furthermore, FasL expressing dendritic cells induced apoptosis in Jurkat and A20 cells. In addition, FasL-transduced dendritic cells inhibited a mixed lymphocyte reaction between allogeneic mouse strains, and FasL-transduced stem-progenitor cells mediated enhanced allogeneic engraftment in vivo. In vivo treatment of mice with FasL-transduced dendritic cells or FasL-transduced stem-progenitor cells was not toxic or globally immunosuppressive. Ongoing studies are being performed to further assess the in vivo applications of the FasL-dendritic cells to tolerize for allogeneic blood and bone marrow transplantation (BMT). Description (Set) Proposed Use (Set) Selective anti-donor tolerization for BMT or transplantation of solid organs Patent (Set) WO 02/072798

Inventor(s): Civin, Curt I.

Type of Offer: Licensing



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