CELLULAR CAMOUFLAGE - FOOLING THE IMMUNE-SYSTEM WITH POLYMERS

Immunological recognition of foreign cells is a primary concern in bot h transfusion and transplantation medicine. Our unique approach to thi s problem is to globally camouflage the surface of the foreign cell us ing nonimmunogenic, long chain polymers such as methoxypoly(ethylene g lycol) [mPEG]. mPEG-modification of red blood cells effectively attenu ates both antibody binding to surface epitopes and decreases the inher ent immunogenicity of foreign, even xenogeneic red cells. These cells exhibit normal structural and functional characteristicsin vitro and e xhibit normal in vivo survival in animal models. Pegylation of white b lood cells (particularly antigen presenting cells and T lymphocytes) s urprisingly prevents recognition of foreign class II molecules and pre vents T cell proliferation in response to foreign MHC molecules. Poten tial applications for the covalent binding of nonimmunogenic, long cha in polymers (e.g., PEG) to intact cells include, but are not limited t o: 1) derivatized RBC to diminish transfusion reactions arising from s ensitization to minor blood group antigens (allosensitization) in the chronically transfused (e.g,, sickle and thalassemia patients); 2) use of mPEG modification of ''passenger'' lymphocytes to prevent immune r ecognition and graft versus host disease; and 3) derivatization of the vascular endothelium of donor tissues prior to transplantation to pre vent/diminish acute tissue rejection. In contrast to highly specific b locking mechanisms (e.g., anti-CD4; proteolytic removal of RBC A/B ant igens), the generation of globally camouflaged (i.e., stealth) cells m ay more effectively prevent the often complex and redundant events lea ding to immune recognition of foreign cells.