Monoclonal antibody additive that inhibits ectodomain shedding of a platelet glycoprotein to improve platelet storage.
- Current storage techniques allows for limited storage times (5-7 days).
- New additive may enable platelet storage at 4°C, increase platelet storage time, and improve quality of stored platelets.
- Inhibits GPB1a shedding, an "aging signal" within platelets, compared to current solutions that simply provide electrolyte, glucose, and buffers to aid in platelet survival.
- Uses an alternative strategy to extend platelet life compared to other technologies.
More than two million doses of donated platelets are transfused annually in the U.S. to treat uncontrolled bleeding or promote healing. It is generally used in cases of trauma, burns, immunodeficiency diseases, certain autoimmune conditions, clotting disorders, cancer or during surgery. In particular, the use of platelet transfusions by surgeons to control bleeding continues to rise. A major challenge however in the effective use of platelets therapeutically is their limited storage life. Current storage techniques consist of constant agitation at 20-24°C, and only allow for a storage time of 5-7 days. Currently available additives do not address storage life or refrigeration of platelets and are focused only on decreasing the volume of plasma required for effective transfusions.
Glycoprotein Ib-alpha (GP1BA) is a membrane protein exclusively expressed on the surface of platelets and is believed to contribute to the short storage life of platelets. The ectodomain of GP1BA is shed via cleavage by metalloproteases, and it has been suggested that shedding of GP1BA plays an important role in the clearance of platelets from the body. Although blocking the activity of the metalloproteases using pharmacological interventions can slow or stop the shedding of GP1BA ectodomain and improve the recovery and survival of mouse platelets, metalloproteases serve many functions within the body and wholesale blockage of their function is not practical as a therapeutic or storage mechanism for humans. In order to circumvent these issues, Dr. Li has created mouse monoclonal antibodies which bind human GP1BA and inhibit its shedding. In modified Chinese Hamster Ovary cells expressing GP1BA, administration of the antibody decreased the level of glycocalicin (the ectodomain portion of GP1BA) and inhibited shedding of GP1BA. With this improvement, this antibody could be added to platelets in storage to increase their lifespan.
- Inhibition of ectodomain shedding was verified in vitro in human platelets and modified CHO cells with GP1BA expression.
- Additional development concerning the process of using and clearing the antibody from stored platelets is underway.
- Demonstration of the antibody to inhibit rapid clearance of refrigerated platelets in animal models is underway.
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