双特异性 T 细胞接合剂 (bsTCE) 已成为一类有前途的癌症免疫疗法。多个bsTCE已获得上市批准；还有数十个正在接受临床研究。然而，bsTCE 的临床开发仍然充满挑战，包括细致入微的药理学、临床前研究结果的有限转化性、频繁的靶向毒性以及复杂的给药方案。在这篇观点文章中，我们对定量系统药理学 (QSP) 如何作为克服这些障碍的强大工具提出了独特的观点。 QSP 建模的最新进展使 bsTCE 的开发人员能够更深入地了解其背景依赖性药理学、弥合实验数据的差距、指导首次人体 (FIH) 剂量选择、设计具有扩展治疗窗的给药方案，并改进长期治疗结果。我们使用最近的案例研究来举例说明 QSP 技术支持未来 bsTCE 开发的潜力。版权所有 © 2023 Elsevier Ltd。保留所有权利。

Bispecific T cell engagers (bsTCEs) have emerged as a promising class of cancer immunotherapy. Several bsTCEs have achieved marketing approval; dozens more are under clinical investigation. However, the clinical development of bsTCEs remains rife with challenges, including nuanced pharmacology, limited translatability of preclinical findings, frequent on-target toxicity, and convoluted dosing regimens. In this opinion article we present a distinct perspective on how quantitative systems pharmacology (QSP) can serve as a powerful tool for overcoming these obstacles. Recent advances in QSP modeling have empowered developers of bsTCEs to gain a deeper understanding of their context-dependent pharmacology, bridge gaps in experimental data, guide first-in-human (FIH) dose selection, design dosing regimens with expanded therapeutic windows, and improve long-term treatment outcomes. We use recent case studies to exemplify the potential of QSP techniques to support future bsTCE development.Copyright © 2023 Elsevier Ltd. All rights reserved.