Abstract:
Chimeric antigen receptor (CAR) cells are genetically engineered immune cells that specifically target tumor-associated antigens and have revolutionized cancer treatment, particularly in hematological malignancies, with ongoing investigations into their potential applications in solid tumors. This review provides a comprehensive overview of the current status and challenges in drug metabolism and pharmacokinetics (DMPK) for CAR cell therapy, specifically emphasizing on quantitative modeling and simulation (M&S). Furthermore, the recent advances in quantitative model analysis have been reviewed, ranging from clinical data characterization to mechanism-based modeling that connects in vitro and in vivo nonclinical and clinical study data. Additionally, the future perspectives and areas for improvement in CAR cell therapy translation have been reviewed. This includes using formulation quality considerations, characterization of appropriate animal models, refinement of in vitro models for bottom-up approaches, and enhancement of quantitative bioanalytical methodology. Addressing these challenges within a DMPK framework is pivotal in facilitating the translation of CAR cell therapy, ultimately enhancing the patients\' lives through efficient CAR cell therapies.
摘要:
嵌合抗原受体(CAR)细胞是基因工程免疫细胞,特异性靶向肿瘤相关抗原,彻底改变了癌症治疗,特别是血液恶性肿瘤,随着对它们在实体瘤中的潜在应用的持续研究。这篇综述全面概述了CAR细胞治疗的药物代谢和药代动力学(DMPK)的现状和挑战,特别强调定量建模和仿真(M&S)。此外,回顾了定量模型分析的最新进展,从临床数据表征到基于机制的建模,连接体外和体内非临床和临床研究数据。此外,回顾了CAR细胞疗法翻译的未来观点和改进领域。这包括使用配方质量考虑,适当动物模型的表征,改进自下而上方法的体外模型,并加强定量生物分析方法。在DMPK框架内应对这些挑战对于促进CAR细胞疗法的转化至关重要。最终通过有效的CAR细胞疗法提高患者的生活。