<scp>Anti‐CD38</scp> monoclonal antibody interference with blood compatibility testing: Differentiating isatuximab and daratumumab via functional epitope mapping

Chami, Btissam; Okuda, Makoto; Moayeri, Morvarid; Pirenne, France; Hidaka, Yoko; Nambiar, Ashok; Song, Zhili; Bedel, Olivier; Zhang, Bailin; Hopke, Joern; Deng, Gejing; Zhu, Chen; Macé, Sandrine; Chiron, Marielle; Adrián, Francisco; Fukao, Takanori; Basile, Frank G.; Martin, Thomas

doi:10.1111/trf.17137

Cited by 8 publications

(1 citation statement)

References 28 publications

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“…Unlike daratumumab, which only produced weak positive panreactivity to panel RBCs [ 1 ], evorpacept produced moderate to strong reactions, even at a low concentration of 0.1 μg/mL. This may be because CD47 is more highly expressed in RBCs than CD38 [ 24 ] and/or the picomolar binding affinity of evorpacept to CD47 [ 28 ] versus nanomolar binding of daratumumab to CD38 [ 31 ]. Additional speculations can be made based on the greater reactivity observed in plasma containing evorpacept compared with daratumumab.…”

Section: Discussionmentioning

confidence: 99%

Evorpacept-Induced Interference and Application of a Novel Mitigation Agent, Evo-NR, in Pretransfusion Testing

Yoon,

Kim,

Kim

et al. 2023

Transfus Med Hemother

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Introduction: Evorpacept is a CD47-blocking agent currently being developed for the treatment of various cancers. Interference by evorpacept in pretransfusion compatibility testing has been reported at limited plasma concentrations. Although various mitigation strategies have been proposed, none are practical. This in vitro study assessed evorpacept-induced interference at extended concentrations and investigated the capability of a novel mitigation agent, Evo-NR. Methods: Antibody screening tests were performed on evorpacept-spiked plasma with (anti-E and anti-Jka) or without alloantibodies at evorpacept concentrations up to 2,000 μg/mL using manual gel cards and automated analyzers. Evorpacept-coated red blood cells (RBCs) (rr [ce/ce], Fy[a+b−], S−s+) were tested by direct antiglobulin testing (DAT) and antigen typing using anti-Fyb and anti-S reagents at indirect antiglobulin testing (IAT) phase. Evo-NR was used to resolve the interference in plasma and RBC samples. Flow cytometry was used to assess the mitigation effects. Results: Evorpacept-spiked plasma showed panreactive interference in antibody screening tests using manual gel cards (2+ to 3+) and automated analyzers (4+). A carryover effect was also observed in the automated analyzers. The use of a 3- to 6-fold molar excess of Evo-NR effectively resolved the interference in the plasma and enabled accurate alloantibody identification. Although the reduction in evorpacept binding to RBCs was identified via flow cytometry, Evo-NR was incapable of resolving the serologic interference observed in DAT and antigen typing at IAT phase. Discussion: Evorpacept showed constant panreactivity and a carryover effect at high concentrations. Evo-NR successfully resolved the interference in the plasma samples and could be considered a practical and efficient mitigation solution. Implementation of Evo-NR has the potential to support RBC transfusion for patients undergoing evorpacept treatment.

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Section: Discussionmentioning

confidence: 99%

Evorpacept-Induced Interference and Application of a Novel Mitigation Agent, Evo-NR, in Pretransfusion Testing

Yoon,

Kim,

Kim

et al. 2023

Transfus Med Hemother

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Immunometabolism: signaling pathways, homeostasis, and therapeutic targets

Xu,

He,

et al. 2024

MedComm

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Immunometabolism plays a central role in sustaining immune system functionality and preserving physiological homeostasis within the organism. During the differentiation and activation, immune cells undergo metabolic reprogramming mediated by complex signaling pathways. Immune cells maintain homeostasis and are influenced by metabolic microenvironmental cues. A series of immunometabolic enzymes modulate immune cell function by metabolizing nutrients and accumulating metabolic products. These enzymes reverse immune cells’ differentiation, disrupt intracellular signaling pathways, and regulate immune responses, thereby influencing disease progression. The huge population of immune metabolic enzymes, the ubiquity, and the complexity of metabolic regulation have kept the immune metabolic mechanisms related to many diseases from being discovered, and what has been revealed so far is only the tip of the iceberg. This review comprehensively summarized the immune metabolic enzymes’ role in multiple immune cells such as T cells, macrophages, natural killer cells, and dendritic cells. By classifying and dissecting the immunometabolism mechanisms and the implications in diseases, summarizing and analyzing advancements in research and clinical applications of the inhibitors targeting these enzymes, this review is intended to provide a new perspective concerning immune metabolic enzymes for understanding the immune system, and offer novel insight into future therapeutic interventions.

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CD38-specific immunoPET imaging for multiple myeloma diagnosis and therapeutic monitoring: preclinical and first-in-human studies

Huang,

Wang,

Qiu

et al. 2024

Eur J Nucl Med Mol Imaging

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Anti‐CD38 monoclonal antibody interference with blood compatibility testing: Differentiating isatuximab and daratumumab via functional epitope mapping

Cited by 8 publications

References 28 publications

Evorpacept-Induced Interference and Application of a Novel Mitigation Agent, Evo-NR, in Pretransfusion Testing

Evorpacept-Induced Interference and Application of a Novel Mitigation Agent, Evo-NR, in Pretransfusion Testing

Immunometabolism: signaling pathways, homeostasis, and therapeutic targets

CD38-specific immunoPET imaging for multiple myeloma diagnosis and therapeutic monitoring: preclinical and first-in-human studies

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