SI14 Stripped Red Cells–Efforts to Eliminate A and B Antigens from the Blood Supply

Abstract

Eliminating the risk for ABO‐incompatible transfusion errors and simplifying blood logistics by creating an ABO‐universal blood inventory is a challenging idea but not a new one. In the early 1980s Goldstein and co‐workers at the New York Blood Centre pioneered the field of enzymatic conversion of blood group B red blood cells (RBC) to group O. They used native or recombinant α‐galactosidase from green coffee beans to remove the immunodominant galactose residues terminally located in the carbohydrate chains found on group B RBC. These enzyme‐converted O (ECO) RBC survived normally in the circulation of individuals independent of the blood group of the recipient. Small infusions were escalated to single, multiple and repeated RBC units. A successful phase II clinical trial in patients was reported in 2000 by Kruskall et al. However, economically unfavourable doses of enzyme were required to convert a unit of blood due to the low pH optimum of the enzyme. Conversion of blood group A cells was never achieved due to lack of A‐converting enzymes working at RBC‐friendly conditions. Also, the chemical nature of group A antigens is more complex due to the A1/A2 subgroups. Following screening of >2500 microorganisms we recently identified a novel family of bacterial exoglycosidases with specificities for the blood group A or B antigens and remarkably improved kinetic properties. Enzymatically converted group A and B RBC type as group O and can now be achieved under cost‐efficient and optimised conditions including neutral pH and room temperature incubation. Clinical trials to evaluate the safety and efficacy of ECO RBC are currently ongoing. Of the different strategies envisioned to create a universal blood component supply, the ECO concept is the only one for which clinical trials in humans have been performed. The presentation will review the current status of this exciting technology and its potential for introduction in the clinical component preparation laboratory. The speaker is a Visiting Associate Professor at Harvard Medical School, Boston, MA, USA and also a scientific consultant to the R&D biotech company ZymeQuest, Inc., Beverly, MA, USA. He gratefully acknowledges the significant and dedicated work performed by numerous members of the ECO team at Copenhagen University, Harvard Medical School, Lund University Hospital Blood Centre and the scientific staff at ZymeQuest.