Novel cell-surface engineering methods to increase immune-tolerance of allogenic cell transplantation

Blood transfusion treats a number of acute and chronic medical problems. In transfusion therapy, unintentional mismatching of red blood cells (RBC) for blood groups remains one of the most common causes of serious and sometimes fatal adverse reactions. In addition, shortage of blood supply in rare blood transfusion and development of alloimmunization in patients undergoing chronic blood transfusions still remains as major challenges to our blood bank system. In the current proposal, this unmet clinical need in blood cell transfusion will be addressed by 1) developing a novel enzyme mediated RBC-surface grafting method, 2) utilizing ‘Factor H’ (negative regulator of complement system—part of innate immune response) binding peptide functionalized hyper-branched polyglycerols (HPG) polymers to protect antigenic sites on the RBC-membrane, and 3) developing combination strategy utilizing polymer grafting to protect minor blood group antigens and enzymatic cleavage of carbohydrate AB antigens to generate truly universal donor RBCs. Such developments would significantly improve the blood supply and increase transfusion safety by successfully modulating the interaction between the modified cells and host immune system. Further, the newly developed method will be applicable in other forms of transplantation medicine by minimizing the adverse immune reaction; hence, evade subsequent rejection or removal.

*Cofunded through a MITACs fellowship

KIZHAKKEDATHU, Jayachandran

University of British Columbia

Graduate Fellowship Program

British Columbia

$82,000