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

IF 6.4 2区医学 Q1 PHARMACOLOGY & PHARMACY

International Journal of Pharmaceutics: X Pub Date : 2025-08-14 DOI:10.1016/j.ijpx.2025.100375

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

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引用次数: 0

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. In vitro efficacy, both MSCs and MSC-BiTE supernatants could induce significant cell death in BT474 and NCIN87 cells. In vivo, 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.

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通过体内表达增强BiTE （HER2/CD3）对HER2阳性肿瘤的治疗效果

双特异性t细胞接合体（bite）是一种小分子抗体，具有强效的杀肿瘤活性，但血浆半衰期短。间充质间质细胞（MSCs）是一种有希望持续表达治疗性蛋白的载体。在这项研究中，我们使用人脐带血-间充质干细胞（hUC-MSCs）作为递送系统来分泌HER2/CD3 BiTE抗体，从而解决了传统BiTE疗法的药代动力学局限性。在多种实体肿瘤中观察到HER2扩增和过表达，使其成为抗癌治疗的有效靶点。因此，我们构建了靶向HER2和CD3的BiTE作为模型。体外效果：MSCs和MSC-BiTE上清液均可诱导BT474和NCIN87细胞显著死亡。在体内，MSC-BiTE抑制NCIN87异种移植瘤模型的肿瘤生长。此外，MSC-BiTE可提高血浆中HER2/CD3抗体水平。因此，MSC-BiTE可能作为一种有效的治疗her2阳性癌症的药物。

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来源期刊

International Journal of Pharmaceutics: X Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science

CiteScore

6.60

自引率

0.00%

发文量

审稿时长

24 days

期刊介绍： International Journal of Pharmaceutics: X offers authors with high-quality research who want to publish in a gold open access journal the opportunity to make their work immediately, permanently, and freely accessible. International Journal of Pharmaceutics: X authors will pay an article publishing charge (APC), have a choice of license options, and retain copyright. Please check the APC here. The journal is indexed in SCOPUS, PUBMED, PMC and DOAJ. The International Journal of Pharmaceutics is the second most cited journal in the "Pharmacy & Pharmacology" category out of 358 journals, being the true home for pharmaceutical scientists concerned with the physical, chemical and biological properties of devices and delivery systems for drugs, vaccines and biologicals, including their design, manufacture and evaluation. This includes evaluation of the properties of drugs, excipients such as surfactants and polymers and novel materials. The journal has special sections on pharmaceutical nanotechnology and personalized medicines, and publishes research papers, reviews, commentaries and letters to the editor as well as special issues.