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人源化抗 Scg3 抗体缓解氧诱导性视网膜病变的最佳疗效和安全性。

Optimal Efficacy and Safety of Humanized Anti-Scg3 Antibody to Alleviate Oxygen-Induced Retinopathy.

机构信息

Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami School of Medicine, Miami, FL 33136, USA.

Everglades Biopharma, LLC, Houston, TX 77054, USA.

出版信息

Int J Mol Sci. 2021 Dec 29;23(1):350. doi: 10.3390/ijms23010350.

Abstract

The retinopathy of prematurity (ROP), a neovascular retinal disorder presenting in premature infants, is the leading causes of blindness in children. Currently, there is no approved drug therapy for ROP in the U.S., highlighting the urgent unmet clinical need for a novel therapeutic to treat the disease. Secretogranin III (Scg3) was recently identified as a disease-selective angiogenic factor, and Scg3-neutralizing monoclonal antibodies were reported to alleviate pathological retinal neovascularization in mouse models. In this study, we characterized the efficacy and safety of a full-length humanized anti-Scg3 antibody (hAb) to ameliorate retinal pathology in oxygen-induced retinopathy (OIR) mice, a surrogate model of ROP, by implementing histological and functional analyses. Our results demonstrate that the anti-Scg3 hAb outperforms the vascular endothelial growth factor inhibitor aflibercept in terms of efficacy and safety to treat OIR mice. Our findings support the development of anti-Scg3 hAb for clinical application.

摘要

早产儿视网膜病变(ROP)是一种发生在早产儿中的新生血管性视网膜疾病,是导致儿童失明的主要原因。目前,美国还没有批准用于 ROP 的药物治疗方法,这突显了迫切需要一种新的治疗方法来治疗这种疾病。分泌颗粒蛋白 III(Scg3)最近被鉴定为一种疾病选择性血管生成因子,并且已经报道 Scg3 中和单克隆抗体可减轻小鼠模型中的病理性视网膜新生血管形成。在这项研究中,我们通过实施组织学和功能分析,描述了全长人源化抗 Scg3 抗体(hAb)改善氧诱导的视网膜病变(OIR)小鼠(ROP 的替代模型)视网膜病理学的功效和安全性。我们的结果表明,抗 Scg3 hAb 在治疗 OIR 小鼠方面的功效和安全性均优于血管内皮生长因子抑制剂阿柏西普。我们的研究结果支持开发抗 Scg3 hAb 用于临床应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e501/8745183/2436e698e2ef/ijms-23-00350-g001.jpg

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