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依斯卡利单抗联合短暂特西多单抗延长猪到恒河猴肾异种移植的存活期。

Iscalimab Combined With Transient Tesidolumab Prolongs Survival in Pig-to-Rhesus Monkey Renal Xenografts.

机构信息

Department of Surgery, University of Minnesota School of Medicine, Minneapolis, Minnesota, USA.

Department of Surgery, Emory University School of Medicine, Atlanta, Georgia, USA.

出版信息

Xenotransplantation. 2024 Jul-Aug;31(4):e12880. doi: 10.1111/xen.12880.

DOI:10.1111/xen.12880
PMID:39185772
Abstract

OBJECTIVE

To evaluate the clinically relevant anti-CD40 antibody iscalimab for baseline immunosuppression in a preclinical pig-to-rhesus renal xenograft model.

SUMMARY BACKGROUND DATA

CD40/CD40L co-stimulation blockade-based immunosuppression has been more successful than calcineurin-based protocols in prolonging xenograft survival in preclinical models.

METHODS

GGTA1 knockout/CD55 transgenic pig kidneys were transplanted into rhesus monkeys (n = 6) receiving an iscalimab-based immunosuppressive regimen.

RESULTS

Two grafts were lost early (22 and 26 days) because of ectatic donor ureters with otherwise normal histology. The other recipients survived 171, 315, 422, and 439 days with good renal function throughout the posttransplant course. None of the recipients experienced serious infectious morbidity.

CONCLUSIONS

It may be reasonable to evaluate an iscalimab-based immunosuppressive regimen in clinical renal xenotransplantation.

摘要

目的

在猪-恒河猴肾异种移植模型中,评估具有临床相关性的抗 CD40 抗体依斯卡利单抗作为基线免疫抑制药物。

背景概要数据

与钙调磷酸酶抑制剂方案相比,基于 CD40/CD40L 共刺激阻断的免疫抑制方案在延长异种移植物存活方面在临床前模型中更为成功。

方法

将 GGTA1 敲除/CD55 转基因猪肾移植到接受依斯卡利单抗免疫抑制方案的恒河猴(n=6)体内。

结果

由于供体输尿管扩张,2 个移植物在早期(22 天和 26 天)丢失,其余组织学正常。其余受者在整个移植后过程中存活了 171、315、422 和 439 天,肾功能良好。受者均未出现严重感染性发病率。

结论

在临床肾异种移植中评估依斯卡利单抗为基础的免疫抑制方案可能是合理的。

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