量化系统药理建模的巨细胞向治疗结合PD-L1抑制在先进的NSCLC
Hanwen Wang1, Theinmozhi Arulraj1, Samira Anbari1
1Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Clinical and translational science
|May 30, 2024
概括
定量系统药理学建模表明,将CCR2抑制剂与抗PD-(L) 1治疗结合起来,可能会改善晚期非小细胞肺癌 (NSCLC) 的结果,与抗CD47不同. 这种方法对抗PD-L) 1阻塞的患者有希望.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 药理学 药理学是指药理学的学科.
背景情况:
- 免疫检查点抑制剂,特别是抗PD-(L) 1,一直是高级非小细胞肺癌 (NSCLC) 的标准,在未经选择的患者中反应率约为20%.
- 开发新的组合疗法对于克服耐药性和提高高级NSCLC治疗疗效至关重要.
研究的目的:
- 开发和应用一个定量系统药理学 (QSP) 模型,以预测巨细胞向疗法的疗效,结合PD-L1抑制在先进的NSCLC.
- 评估抗CD47和CCR2抑制作为与抗PD-(L) 1治疗的组合策略.
主要方法:
- 开发了一个药理动力学/药理动力学模块,集成到之前存在的QSP模型中.
- 在 silico 临床试验中进行,以模拟先进的 NSCLC 模型中的治疗反应.
- 评估的组合疗法包括抗PD-(L) 1与抗CD47或CCR2抑制剂.
主要成果:
- 在 silico 试验中表明,抗CD47在PD-L) 1 耐药高级NSCLC的第二线或后一线治疗中是不理想的.
- 预测,抑制巨细胞的招募 (例如,CCR2抑制剂) 与抗PD-(L) 1疗法相结合可以增强瘤的减少.
- 确定的患者子组 (对抗PD-L1单一治疗的响应者,高瘤相关的巨细胞) 可能受益于CCR2抑制组合.
结论:
- 该QSP平台有效地预测了在先进NSCLC中新药组合疗效.
- 与抗PD-(L) 1治疗相结合的CCR2抑制显示出改善治疗结果的潜力,特别是在特定患者群体中.
- 在这种情况下,不建议使用Anti-CD47作为后续疗法.
更多相关视频
10:29Semi-automatic PD-L1 Characterization and Enumeration of Circulating Tumor Cells from Non-small Cell Lung Cancer Patients by Immunofluorescence
Published on: August 14, 2019
10.6K
06:07Monitoring PD-1-Blocking Antibodies Bound to T Cells Derived from a Drop of Peripheral Blood
Published on: February 5, 2020
5.7K
相关概念视频
01:27Pharmacodynamic Models: Overview
Pharmacodynamic (PD) responses describe the interaction between a drug and its biological target, culminating in a physiological effect. These responses can be classified into different types: continuous variables, such as blood glucose levels; categorical outcomes, like survival rates; and time-to-event metrics, such as disease progression. Understanding and modeling PD responses are critical for optimizing drug efficacy and safety.PD models describe the relationship between drug concentration...
01:15Impact of Pharmacokinetic–Pharmacodynamic Models: Regulatory Decisions
PK–PD modeling has significantly influenced FDA regulatory decisions, particularly drug approval, dosage optimization, and labeling. These models integrate pharmacokinetics (PK) and pharmacodynamics (PD) to predict drug behavior and effects, aiding in optimizing dosing regimens and enhancing the probability of clinical trial success.One notable example is Nesiritide (Natrecor®), a recombinant human brain natriuretic peptide for treating acute decompensated congestive heart failure (CHF).