Cellular Camouflage: Fooling the Immune System with Polymers

Abstract

Immunological recognition of foreign cells is a primary concern in both transfusion and transplantation medicine. Our unique approach to this problem is to globally camouflage the surface of the foreign cell using nonimmunogenic, long chain polymers such as methoxypoly(ethylene glycol) [mPEG]. mPEG-modification of red blood cells effectively attenuates both antibody binding to surface epitopes and decreases the inherent immunogenicity of foreign, even xenogeneic red cells. These cells exhibit normal structural and functional characteristicsin vitro and exhibit normal in vivo survival in animal models. Pegylation of white blood cells (particularly antigen presenting cells and T lymphocytes) surprisingly prevents recognition of foreign class II molecules and prevents T cell proliferation in response to foreign MHC molecules. Potential applications for the covalent binding of nonimmunogenic, long chain polymers (e.g., PEG) to intact cells include, but are not limited to: 1) derivatized RBC to diminish transfusion reactions arising from sensitization 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 recognition and graft versus host disease; and 3) derivatization of the vascular endothelium of donor tissues prior to transplantation to prevent/diminish acute tissue rejection. In contrast to highly specific blocking mechanisms (e.g., anti-CD4; proteolytic removal of RBC A/B antigens), the generation of globally camouflaged (i.e., stealth) cells may more effectively prevent the often complex and redundant events leading to immune recognition of foreign cells.