Progress in modulating the RBC membrane to produce transfusable universal/stealth donor RBCs

Two approaches have been used to produce red blood cells (RBCs) that could be transfused, regardless of the ABO group of the donor and recipient, the so-called "universal donor" RBCs. The first approach has involved converting group A and B RBCs to group O by cleaving off the terminal immunodominant sugars; the second approach involves masking the A and B antigens with polyethylene glycol (PEG). The latter approach has also been used to mask all other blood group antigens on the RBC membrane, yielding so-called "stealth RBCs"; the hope is that such PEGylated RBCs (PEG-RBCs) will not react with any blood group antibodies and may not be recognized as foreign, thus not initiating an immune response. The former approach is well advanced. Clinical trials have shown that units of group B blood converted to group O, using a galactosidase, survived normally without any ill effects to recipients. Work is progressing on the efficient conversion of group A RBCs to group O. PEG-RBCs can be prepared that will not react with any blood group antibodies in vitro, but RBC survival in animals has not been good. Recent data show that PEG is immunogenic and can induce antibodies that shorten survival of transfused PEG-RBCs in rabbits.