MODIFIED CELLS AND METHODS FOR INHIBITING HYPERACUTE REJECTION OF XENOGENEIC TRANSPLANTS

摘要

Modified cells for transplantation having reduced capacity to stimulate natural antibody-mediated hyperacute rejection of the cell in a transplant recipient are disclosed. In unmodified form, cells for use in xenogeneic transplantation express at least one epitope on a cell surface antigen which is bound by natural antibodies in a recipient. Prior to transplantation, the cells are modified to alter, reduce or substantially eliminate expression of the epitope on the cell surface. Preferably, the cell is a porcine cell and the epitope is a galactosyl (α1,3) galactose epitope. Methods for reducing the immunogenicity of a cell for transplantation into a recipient are also disclosed. Modified cells of the invention can additionally be treated to alter, reduce or substantially eliminate another surface antigen (e.g., an MHC class I antigen) which stimulates a cellular immune response against the cell in a recipient. Additionally, a recipient can be treated with an agent which inhibits T cell activity, such as an immunosuppressive drug or an anti-T cell antibody.