Immunotherapy, the use of humanized monoclonal antibodies, is a promising therapy that works in conjunction with the patient’s own immune system to target and mark cancerous cells for destruction. Anti-CD38, or daratumumab, targets the CD38 protein expressed on certain types of cancer cells. Anti-CD38, unfortunately, also interferes with serological testing. CD38, luckily, can be denatured with dithiothreitol (DTT) allowing for subsequent alloantibody testing. A new monoclonal IgG4 antibody, anti-CD47 (Hu5F9-G4) is currently in clinical trials for treatment of hematologic and solid malignancies. CD47 is a glycoprotein expressed on all cells including RBCs and platelets, which usually signals to prevent phagocytosis. Anti-CD47 blocks this signal targeting cells for destruction. Researchers recently investigated the interference of this new drug in pre-transfusion serological testing using samples from four patients taking anti-CD47. Anti-CD47 interfered with all RBC and platelet serological tests performed including ABO reverse typing. In addition, CD47 could not be denatured with DDT or other common denaturing agents. The best mitigation strategy for blood bankers includes requesting drug history for patients requiring transfusions, performing multiple RBC alloadsorptions, and using monoclonal Gamma-clone IgG in indirect antigen testing (which does not detect IgG4s like anti-CD47). Practical and cost-effective approaches for serological testing for patients taking anti-CD47 need further investigation.
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