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通过表达增强双特异性T细胞衔接器(HER2/CD3)对HER2阳性肿瘤的治疗效果。

Enhance therapeutic efficacy of BiTE (HER2/CD3) for HER2- positive tumors through expression.

作者信息

Zong Huifang, Li Xi, Li Yunxia, Wang Lei, Yue Yali, Chen Jie, Ke Yong, Paerhati Pameila, Han Lei, Li Yijia, Zhu Jianwei, Zhang Baohong

机构信息

Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, China, School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.

Jecho Institute, Co. Ltd., Shanghai 200240, China.

出版信息

Int J Pharm X. 2025 Aug 14;10:100375. doi: 10.1016/j.ijpx.2025.100375. eCollection 2025 Dec.

Abstract

Bispecific T-cell engagers (BiTEs) are small-molecule antibodies that exhibits potent tumoricidal activity but suffer from a short plasma half-life. Mesenchymal stromal cells (MSCs) represent promising delivery vehicles for sustained therapeutic protein expression. In this study, we used human umbilical cord blood-MSCs (hUC-MSCs) as a delivery system to to secrete HER2/CD3 BiTE antibodies, thereby addressing the pharmacokinetic limitations of conventional BiTE therapies. HER2 amplification and overexpression are observed in multiple solid tumors, making it a potent target for anti-cancer therapies. Therefore, we constructed a BiTE targeting HER2 and CD3 as a model. efficacy, both MSCs and MSC-BiTE supernatants could induce significant cell death in BT474 and NCIN87 cells. , MSC-BiTE inhibited tumor growth in NCIN87 xenograft model. Furthermore, MSC-BiTE elevated the plasma levels of BiTE (HER2/CD3) antibody. Therefore, MSC-BiTE may be used as an efficient therapeutic agent for HER2-positive cancers.

摘要

双特异性T细胞衔接器(BiTEs)是一种小分子抗体,具有强大的杀瘤活性,但血浆半衰期较短。间充质基质细胞(MSCs)是持续治疗性蛋白表达的有前景的递送载体。在本研究中,我们使用人脐带血间充质基质细胞(hUC-MSCs)作为递送系统来分泌HER2/CD3 BiTE抗体,从而解决传统BiTE疗法的药代动力学限制。在多种实体瘤中观察到HER2扩增和过表达,使其成为抗癌治疗的有效靶点。因此,我们构建了一种靶向HER2和CD3的BiTE作为模型。在疗效方面,间充质基质细胞和间充质基质细胞-BiTE上清液均可在BT474和NCI-N87细胞中诱导显著的细胞死亡。此外,间充质基质细胞-BiTE在NCI-N87异种移植模型中抑制肿瘤生长。而且,间充质基质细胞-BiTE提高了BiTE(HER2/CD3)抗体的血浆水平。因此,间充质基质细胞-BiTE可能用作HER2阳性癌症的有效治疗剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5584/12410412/c6428f8408c8/gr1.jpg

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