CHEMICAL CAMOUFLAGE OF ANTIGENIC DETERMINANTS - STEALTH ERYTHROCYTES

In a number of clinical circumstances it would be desirable to artific ially conceal cellular antigenic determinants to permit survival of he terologous donor cells. A case in point is the problem encountered in transfusions of patients with rare blood types or chronically transfus ed patients who become allosensitized to minor blood group determinant s. We have tested the possibility that chemical modification of the re d blood cell (RBC) membrane might serve to occlude antigenic determina nts, thereby minimizing transfusion reactions. To this end, we have co valently bound methoxy(polyethylene glycol) (mPEG) to the surface of m ammalian RBC via cyanuric chloride coupling. Human RBC treated with th is technique lose ABO blood group reactivity as assessed by solution-p hase antisera agglutination. In accord with this, we also find a profo und decrease in anti-blood group antibody binding. Furthermore, wherea s human monocytes avidly phagocytose untreated sheep RBC, mPEG-derivat ized sheep RBC are ineffectively phagocytosed. Surprisingly, human and mouse RBC appear unaffected by this covalent modification of the cell membrane. Thus, mPEG-treated RBC are morphologically normal, have nor mal osmotic fragility, and mPEG-derivatized murine RBC have normal in vivo survival, even following repeated infusions. Finally, in prelimin ary experiments, mPEG-modified sheep RBC intraperitoneally transfused into mice show significantly improved (up to 360-fold) survival when c ompared with untreated sheep RBC. We speculate that similar chemical c amouflage of intact cells may have significant clinical applications i n both transfusion (e.g., allosensitization and autoimmune hemolytic d isease) and transplantation (e.g., endothelial cells and pancreatic be ta cells) medicine.