PDF(Pubmed)
Abstract：
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
摘要：
Evorpacept是目前正在开发用于治疗各种癌症的CD47阻断剂。据报道，在有限的血浆浓度下，evorpacept对输血前相容性测试的干扰。尽管已经提出了各种缓解策略，没有一个是实际的。这项体外研究评估了在扩展浓度下evorpacept诱导的干扰，并研究了新型缓解剂的能力，Evo-NR.
使用手动凝胶卡和自动分析仪，在evorpacept浓度高达2,000μg/mL的含（抗E和抗Jka）或不含同种抗体的血浆中进行抗体筛选测试。Evorpacept包被的红细胞（RBC）（rr[ce/ce]，Fy[a+b-],在间接抗球蛋白测试（IAT）阶段，通过直接抗球蛋白测试（DAT）和使用抗Fyb和抗S试剂的抗原分型来测试S-s）。Evo-NR用于解决血浆和RBC样品中的干扰。流式细胞术用于评估缓解效果。
■在使用手动凝胶卡(2+至3+)和自动分析仪(4+)的抗体筛选测试中,Evorpacept-spined血浆显示全反应性干扰。在自动分析仪中也观察到残留效应。使用3至6倍摩尔过量的Evo-NR有效地解决了血浆中的干扰，并能够进行准确的同种抗体鉴定。尽管通过流式细胞术鉴定了evorpacept与红细胞结合的减少，Evo-NR无法解决在DAT和IAT期抗原分型中观察到的血清学干扰。
■Evorpacept在高浓度下显示出恒定的泛反应性和残留效应。Evo-NR成功地解决了血浆样品中的干扰，并且可以被认为是一种实用且有效的缓解解决方案。实施Evo-NR有可能支持接受evorpacept治疗的患者的红细胞输注。
使用手动凝胶卡和自动分析仪，在evorpacept浓度高达2,000μg/mL的含（抗E和抗Jka）或不含同种抗体的血浆中进行抗体筛选测试。Evorpacept包被的红细胞（RBC）（rr[ce/ce]，Fy[a+b-],在间接抗球蛋白测试（IAT）阶段，通过直接抗球蛋白测试（DAT）和使用抗Fyb和抗S试剂的抗原分型来测试S-s）。Evo-NR用于解决血浆和RBC样品中的干扰。流式细胞术用于评估缓解效果。
■在使用手动凝胶卡(2+至3+)和自动分析仪(4+)的抗体筛选测试中,Evorpacept-spined血浆显示全反应性干扰。在自动分析仪中也观察到残留效应。使用3至6倍摩尔过量的Evo-NR有效地解决了血浆中的干扰，并能够进行准确的同种抗体鉴定。尽管通过流式细胞术鉴定了evorpacept与红细胞结合的减少，Evo-NR无法解决在DAT和IAT期抗原分型中观察到的血清学干扰。
■Evorpacept在高浓度下显示出恒定的泛反应性和残留效应。Evo-NR成功地解决了血浆样品中的干扰，并且可以被认为是一种实用且有效的缓解解决方案。实施Evo-NR有可能支持接受evorpacept治疗的患者的红细胞输注。
