Assessing and mitigating the interference of ALX148, a novel CD47 blocking agent, in pretransfusion compatibility testing.
ALX148
CD47 blocking agents
Hu5F9-G4
high-affinity SIRPα monomers
interference
pretransfusion compatibility testing
soluble CD47
Journal
Transfusion
ISSN: 1537-2995
Titre abrégé: Transfusion
Pays: United States
ID NLM: 0417360
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
10
12
2019
revised:
13
06
2020
accepted:
30
06
2020
pubmed:
21
8
2020
medline:
30
6
2021
entrez:
22
8
2020
Statut:
ppublish
Résumé
ALX148, a novel CD47 blocking agent, is in clinical development for the treatment of advanced solid tumors and lymphoma. Because CD47 is highly expressed on red blood cells (RBCs), its therapeutic blockade can potentially interfere with pretransfusion compatibility testing. This study describes the interference of ALX148 in pretransfusion compatibility testing and evaluates the methods used for mitigating such interference. Routine serologic tests were performed on six samples from four patients treated with ALX148. Antibody screening tests were performed on ALX148-spiked plasma, and RBC testing including antigen typing was performed on ALX148-coated RBCs. Soluble CD47 or high-affinity signal regulatory protein α (SIRPα) monomers were used to remove the false-positive reactivity of ALX148-spiked plasma with or without anti-E. ALX148 caused false-positive reactivity in antibody screening using indirect antiglobulin testing (IAT) and two-stage papain testing. However, false-positive reactivity was not observed at the immediate spin (IS), room temperature (RT), and 37°C phases. Direct antiglobulin testing, autologous controls, and eluates showed positive results. ALX148 did not affect blood group antigen typing performed at the IS or RT phases. The use of 50- to 100-fold molar excess of soluble CD47 or 300-fold molar excess of high-affinity SIRPα monomers removed false-positive reactivity in IAT without affecting anti-E detection. ALX148 generates false-positive reactivity in IAT, interfering with pretransfusion compatibility testing. The use of soluble CD47 or high-affinity SIRPα monomers can resolve the interference without possibly missing clinically significant alloantibodies.
Substances chimiques
ALX148
0
Antineoplastic Agents
0
CD47 Antigen
0
CD47 protein, human
0
Immunoglobulin Fc Fragments
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2399-2407Subventions
Organisme : ALX148, soluble CD47, and high-affinity SIRPα monomers were provided by ALX Oncology.
Organisme : ALX148, soluble CD47, and high-affinity SIRPα monomers were provided by ALX Oncology
Informations de copyright
© 2020 AABB.
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