Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Trends Pharmacol Sci. 2023 Dec;44(12):880-890. doi: 10.1016/j.tips.2023.09.009. Epub 2023 Oct 17.
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.
双特异性 T 细胞衔接器（bsTCE）已成为一类有前途的癌症免疫疗法。有几种 bsTCE 已获得市场批准；还有数十种正在临床研究中。然而，bsTCE 的临床开发仍然充满挑战，包括细微的药理学、临床前发现的有限可转化性、频繁的靶毒性和复杂的给药方案。在这篇观点文章中，我们提出了一个不同的观点，即定量系统药理学（QSP）如何可以作为克服这些障碍的强大工具。QSP 建模的最新进展使 bsTCE 的开发者能够更深入地了解其与上下文相关的药理学，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口的给药方案，并改善长期治疗效果。我们使用最近的案例研究来说明 QSP 技术支持未来 bsTCE 开发的潜力。
