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Grant: Operating Grant

University of British Columbia

$731,651.00

Novel Cell Surface Engineering Approaches for Cell-based Therapies

FY 2013-14

Summary
Blood transfusion is a valuable tool in modern medicine and is very important to the health of surgery patients, sickle cell patients, thalassemia and cancer patients. In current blood banking procedures, blood typing ensures the safety of patients as mismatched blood transfusion can be very dangerous, however, it is continuously occurring. In certain group of patients who receive frequent blood transfusion (25 to 50 blood units/year) (e.g. thalassemia, sickle cell and myelodysplastic syndromes patients) develop mild to severe immune reactions due to mismatch of minor antigens (>300 on RBCs) which are not usually typed in current blood bank protocols. Transfusion can be challenging to these patients. There is no method currently available to address this unmet clinical need. In this project, we are developing a novel cell-surface modification method for the creation of universal donor blood cells. Using cell compatible and biomimetic polymers, we are creating a polymer shield on RBC surface to mask the recognition of low lying protein based minor blood group antigens (>300 of them on cell surface) by the body. This will be combined with newly developed highly active and selective enzymes which can completely remove the carbohydrate based blood group antigens (A and B) which extend farther on the cell surface at room temperature and physiological conditions for the creation of a truly universal donor blood cells which can be transfused to any patients without blood typing. The development of such technology will be a fundamental advance and will tremendously improve our national blood supply and transfusion safety. The developed cell-modification methods will be readily applicable to other therapies which use living cells (e.g. in the treatment of immunological disorders and cancer) to increase their efficacy in the body and in other forms of transplantation.
Program
Operating Grant
Location
British Columbia, Canada
Recipient Type
Academia
Type
Grant
Source
CIHR Funding Decisions Database

As published

Id
304935
Name
Kizhakkedathu Jayachandran N
Region
British Columbia
Country
Canada
Orgtype
Institution Paid; Research Institution
Instname2
Circulatory and Respiratory Health
Theme2
Biomedical
Prcname2
Biomedical Engineering
Projecttitle
Novel Cell Surface Engineering Approaches for Cell-based Therapies
Programtype2
Operating Grants
Orgnameinp2
University of British Columbia
Cihramount2
$731,651
Cihrequipment2
$0
Programname2
Operating Grant
Keyworddelim
Antigen Masking; Blood Transufsion; Cell-Based Therapies; Cell-Surface Engineering; Directed Enzyme Evolution; Glycosidases; Polymer Grafting; Polymer Synthesis; Protein Engineering; Universal Blood Cells
Abstract
Blood transfusion is a valuable tool in modern medicine and is very important to the health of surgery patients, sickle cell patients, thalassemia and cancer patients. In current blood banking procedures, blood typing ensures the safety of patients as mismatched blood transfusion can be very dangerous, however, it is continuously occurring. In certain group of patients who receive frequent blood transfusion (25 to 50 blood units/year) (e.g. thalassemia, sickle cell and myelodysplastic syndromes patients) develop mild to severe immune reactions due to mismatch of minor antigens (>300 on RBCs) which are not usually typed in current blood bank protocols. Transfusion can be challenging to these patients. There is no method currently available to address this unmet clinical need. In this project, we are developing a novel cell-surface modification method for the creation of universal donor blood cells. Using cell compatible and biomimetic polymers, we are creating a polymer shield on RBC surface to mask the recognition of low lying protein based minor blood group antigens (>300 of them on cell surface) by the body. This will be combined with newly developed highly active and selective enzymes which can completely remove the carbohydrate based blood group antigens (A and B) which extend farther on the cell surface at room temperature and physiological conditions for the creation of a truly universal donor blood cells which can be transfused to any patients without blood typing. The development of such technology will be a fundamental advance and will tremendously improve our national blood supply and transfusion safety. The developed cell-modification methods will be readily applicable to other therapies which use living cells (e.g. in the treatment of immunological disorders and cancer) to increase their efficacy in the body and in other forms of transplantation.
Competitiondate
201403
Approvedterm2
5 yrs 0 mth
Pinamesdelim
Kizhakkedathu, Jayachandran N
Approvedterm
5 ans 0 mois
Cihrcontribution2
~ $731,651~ $0~