溶瘤病毒-CAR-T细胞联合治疗的随机脉冲动力学模型及其平稳分布

Stochastic Impulsive Dynamical Model and Stationary Distribution of Oncolytic Virus-CAR-T Cell Combination Therapy

摘要: 近年来，溶瘤病毒与CAR-T细胞联合治疗在癌症免疫治疗领域展现出广阔的应用前景。本研究构建了具有脉冲输注和随机扰动的肿瘤免疫动力学模型，探讨CAR-T细胞在溶瘤病毒联合治疗中的作用机制。通过构造辅助函数，建立了系统存在唯一遍历平稳分布的条件，并推导出CAR-T细胞脉冲输注次数的约束条件。结果表明，输注频率过高可能降低疗效甚至产生负面影响，强调合理控制输注频率的重要性。该研究为优化CAR-T细胞治疗方案提供数学依据，有助于提高联合治疗的临床效果。

Abstract: In recent years, the combination of oncolytic viruses (OVs) and chimeric antigen receptor T (CAR-T) cells has shown a broad application prospect in cancer immunotherapy. This study develops a tumor immunodynamic model incorporating pulse infusion and stochastic perturbations to investigate the mechanistic role of CAR-T cells in OV-based combination therapy. By constructing an auxiliary function, we establish conditions ensuring the existence of a unique ergodic stationary distribution and derive constraints on the frequency of CAR-T cell pulse infusions. The results indicate that excessively frequent infusions may diminish therapeutic efficacy or even induce adverse effects, highlighting the importance of optimizing infusion schedules. This study provides a mathematical foundation for refining CAR-T cell treatment strategies, contributing to the enhancement of clinical outcomes in combination therapy.