Comparative efficacy of blood cell immunocamouflage by membrane grafting of methoxypoly(ethylene glycol) and polyethyloxazoline

The grafting of low-immunogenic polymers to cells dramatically reduces antigenic recognition and immunogenicity of allogeneic donor cells consequent to steric and charge camouflage (i.e., immunocamouflage). While methoxypoly(ethylene glycol) [mPEG] has historically been utilized for the immunocamouflage of cells, other low-immunogenic polymers such as polyethyloxazoline propionic acid (PEOZ) may also be capable of conferring immunoprotection. Moreover, PEOZ may have attributes that could have enhanced pharmacological and biological utility relative to mPEG. To evaluate the immunocamouflage efficacy of PEOZ relative to mPEG, human red blood cells (RBC) and leukocytes were modified with mPEG or PEOZ. The differential effects of mPEG and PEOZ was assessed via grafting efficacy, cell morphology and viability, immunocamouflage of surface antigens, and the prevention of in vitro immune recognition (RhD and HLA). Although membrane grafting of mPEG and PEOZ were similar, mPEG demonstrated superior immunocamouflage efficacy as measured by antibody binding and phagocytosis of opsonized RBC while PEOZ showed improved RBC morphology. While mPEG appears to be superior to PEOZ in the immunocamouflage of cells, PEOZ may still be a valuable addition to our repertoire of immunomodulatory polymers. Moreover, our results demonstrate the importance of indirect immunocamouflage of antigens found in membrane protein complexes.