Zong Huifang, Li Xi, Li Yunxia, Wang Lei, Yue Yali, Chen Jie, Ke Yong, Paerhati Pameila, Han Lei, Li Yijia, Zhu Jianwei, Zhang Baohong
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.
Int J Pharm X. 2025 Aug 14;10:100375. doi: 10.1016/j.ijpx.2025.100375. eCollection 2025 Dec.
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.
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。