Mathematical Biosciences最新文献_第6页

Modeling cholera transmission dynamics with antibiotic resistance and mutation: A case study in Zimbabwe 模拟霍乱传播动力学与抗生素耐药性和突变：在津巴布韦的一个案例研究

IF 1.8 4区数学 Q2 BIOLOGY

Mathematical Biosciences

Pub Date : 2025-10-01 DOI: 10.1016/j.mbs.2025.109545

Wei Wang , Yuan Lou , Xiunan Wang

Cholera remains a significant cause of morbidity and mortality worldwide. Although antibiotic use can reduce transmission, misuse, overuse, or incomplete treatment can foster the emergence of antibiotic resistance. Selective pressure plays a crucial role in shaping the dynamics of resistance in

V i b r i o c h o l e r a e

, particularly by increasing the mutation rate that transforms antibiotic-sensitive strains into resistant ones. In this study, we develop a novel mathematical model to investigate the impact of antibiotic resistance on cholera transmission dynamics. We establish the existence and stability of equilibria and fit the model to cholera outbreak data from Zimbabwe. Our results reveal a critical interplay between mutation rates and strain fitness: when resistant strains have low reproductive fitness, increased mutation rates alone fail to establish their dominance; however, when resistance carries a fitness advantage, higher mutation rates trigger a regime shift to resistant strain dominance—a newly identified phenomenon with implications for resistance management. We further demonstrate that incomplete treatment (lower recovery rates) exacerbates resistance by prolonging antibiotic exposure. Crucially, our findings underscore that judicious antibiotic use can simultaneously curb resistance emergence and outbreak spread in Zimbabwe, offering actionable insights for public health strategies.

霍乱仍然是全世界发病率和死亡率的一个重要原因。虽然使用抗生素可减少传播，但滥用、过度使用或治疗不完全可促进抗生素耐药性的出现。选择压力在形成霍乱弧菌耐药动态方面起着至关重要的作用，特别是通过增加将抗生素敏感菌株转变为耐药菌株的突变率。在这项研究中，我们开发了一个新的数学模型来研究抗生素耐药性对霍乱传播动力学的影响。我们建立了均衡的存在性和稳定性，并将模型拟合到津巴布韦的霍乱暴发数据中。我们的研究结果揭示了突变率和菌株适应度之间的关键相互作用：当抗性菌株的生殖适应度较低时，单独增加突变率无法建立其优势地位；然而，当抗性具有适应性优势时，较高的突变率会引发抗性品系的统治性转变——这是一种新发现的现象，对抗性管理具有启示意义。我们进一步证明不完全治疗（较低的恢复率）通过延长抗生素暴露加剧了耐药性。至关重要的是，我们的研究结果强调，明智地使用抗生素可以同时遏制津巴布韦耐药性的出现和疫情蔓延，为公共卫生战略提供可行的见解。

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引用次数: 0

Model formulation and oscillatory patterns in immune-pathogen dynamics during Brucellosis infection 布鲁氏菌感染期间免疫-病原体动力学的模型制定和振荡模式。

IF 1.8 4区数学 Q2 BIOLOGY

Mathematical Biosciences

Pub Date : 2025-09-30 DOI: 10.1016/j.mbs.2025.109543

Zehui Li , Junpeng Liu , Linhua Zhou , Chunhua Shan , Meng Fan

Brucellosis, a global zoonosis imposing major health and economic burdens, is clinically marked by recurrent undulant fever linked to Brucella’s persistence within macrophages. To decipher the immune-pathogen dynamics underlying this fever periodicity, this study develops a novel mathematical model that integrates macrophage self-renewal, logistic growth constrained by cellular carrying capacity, and intracellular Brucella replication. Stability and bifurcation analyses reveal two crucial thresholds: one for infection persistence, requiring

R_{0} > 1

, and another for the emergence of undulant fever, triggered by a supercritical Hopf bifurcation. This bifurcation occurs when the macrophage self-renewal rate (

r

) surpasses its mortality rate (

d

) and the infection rate (

θ

) lies in a critical range, marking a transition from stable equilibrium to stable limit cycles. These periodic oscillations, stemming from a dynamic imbalance between immune regeneration and bacterial proliferation, provide a direct mechanistic explanation for recurrent febrile episodes. Counterintuitively, excessive macrophage renewal or carrying capacity can destabilize the system, exacerbating febrile cycles. Our findings posit that interventions simultaneously preventing immune resource exhaustion and curbing intracellular bacterial survival could suppress these pathological oscillations, thereby proposing novel perspectives for managing chronic brucellosis.

布鲁氏菌病是一种全球性的人畜共患病，对健康和经济造成重大负担，其临床特征是与布鲁氏菌在巨噬细胞内持续存在有关的反复波状热。为了解释这种发烧周期性背后的免疫-病原体动力学，本研究建立了一个新的数学模型，该模型集成了巨噬细胞自我更新、受细胞携带能力约束的逻辑生长和细胞内布鲁氏菌复制。稳定性和分岔分析揭示了两个关键阈值：一个是感染持续性阈值，需要R0 bbb1，另一个是出现波状热阈值，由超临界Hopf分岔触发。当巨噬细胞自我更新率(r)超过其死亡率(d)，侵染率（θ）处于临界范围时，巨噬细胞从稳定平衡向稳定极限环过渡。这些周期性振荡源于免疫再生和细菌增殖之间的动态不平衡，为反复发热发作提供了直接的机制解释。与直觉相反，过度的巨噬细胞更新或承载能力会破坏系统的稳定，加剧发热周期。我们的研究结果表明，同时防止免疫资源耗尽和抑制细胞内细菌存活的干预措施可以抑制这些病理振荡，从而为治疗慢性布鲁氏菌病提出了新的视角。

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引用次数: 0

Spatio-temporal modeling and analysis of two HIV strain infections via demographic–geographic data 基于人口地理数据的两种HIV毒株感染的时空建模和分析。

IF 1.8 4区数学 Q2 BIOLOGY

Mathematical Biosciences

Pub Date : 2025-09-29 DOI: 10.1016/j.mbs.2025.109539

Peng Wu , Tong Chen , Shigui Ruan

The emergence of drug resistance poses a significant challenge to the clinical treatment of HIV/AIDS, making the spread of drug-resistant strains among the infected population a key focus in the monitoring and control of HIV/AIDS. In this paper, we construct a reaction–diffusion model with two HIV strains (drug-sensitive and drug-resistant) to study the spatio-temporal dynamics of HIV/AIDS transmission. With spatial heterogeneity, we derive the basic reproduction number

R_{0}

and show that it is a threshold for the outbreak of the disease; that is, when

R_{0} < 1

the disease will eventually die out, while when

R_{0} > 1

the disease is uniformly persistent. In particular, when the model parameters are independent of the space variable, global stability of the infection equilibrium is proven by constructing an appropriate Lyapunov functional. In the numerical simulation part, we discuss the traveling wave phenomenon of HIV/AIDS infection in the population under different diffusion forms and different initial value distributions. We combine the population statistical data, geographical data, and data of different strain infection cases in Zhejiang Province, China, and simulate the spatial spread of HIV/AIDS in Zhejiang Province through the finite element method with the aid of COMSOL Multiphysics software. This provides a new perspective to analyze the impact of dispersal on the spatio-temporal transmission of HIV/AIDS. Numerical simulations show that: (i) High adherence to treatment can effectively reduce the proportion of acquired drug-resistant cases among the total number of cases; (ii) The form of population diffusion has a huge impact on the spatio-temporal transmission of HIV/AIDS, which means that population movement will be one of the important contents of HIV/AIDS prevention and monitoring; (iii) Ignoring the differences in population movement will misjudge the overall trend of HIV/AIDS in the region, so the differences in spatial diffusion in HIV/AIDS prevention and control cannot be ignored.

耐药性的出现对艾滋病毒/艾滋病的临床治疗构成重大挑战，使耐药菌株在受感染人群中的传播成为监测和控制艾滋病毒/艾滋病的一个关键重点。本文构建了两种HIV毒株（药敏和耐药）的反应扩散模型，研究了HIV/AIDS传播的时空动态。考虑到空间异质性，导出了基本繁殖数R0，并表明R0是疾病爆发的阈值；也就是说，当R00 bb01时，疾病是均匀持续的。特别地，当模型参数与空间变量无关时，通过构造适当的Lyapunov泛函证明了感染平衡点的全局稳定性。在数值模拟部分，我们讨论了不同扩散形式和不同初始值分布下人群中HIV/AIDS感染的行波现象。本文结合浙江省人口统计数据、地理数据和不同毒株感染病例数据，借助COMSOL Multiphysics软件，通过有限元方法模拟了浙江省HIV/AIDS的空间传播。这为分析传播对HIV/AIDS时空传播的影响提供了新的视角。数值模拟结果表明：(1)高依从性治疗可有效降低获得性耐药病例占总病例的比例；（二）人口扩散形式对HIV/AIDS的时空传播具有巨大影响，人口流动将成为HIV/AIDS预防和监测的重要内容之一；（三）忽视人口流动的差异会误判区域HIV/AIDS的总体趋势，因此HIV/AIDS防控的空间扩散差异不容忽视。

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引用次数: 0

A mathematical model for cancer dynamics with treatment and saboteur bacteria 癌症动力学与治疗和破坏细菌的数学模型

IF 1.8 4区数学 Q2 BIOLOGY

Mathematical Biosciences

Pub Date : 2025-09-26 DOI: 10.1016/j.mbs.2025.109541

Anna Geretovszky , Gergely Röst

We construct a mathematical model of cancer dynamics with chemotherapeutic treatment, in the presence of bacteria that are capable of metabolizing the chemotherapeutic drug, hence sabotaging the treatment. We investigate the possibility of complementing the cancer treatment with antibiotic drugs, thus eradicating the bacteria or at least mitigating their negative impact on the prospects of therapy. Our model is a nonlinear system of four differential equations, for which we perform a complete analysis, explicitly characterizing the four possible outcomes, depending on whether the cancer cells or the bacteria become extinct or persist. Global stability results are proven by the iterative application of a comparison principle, and a bifurcation diagram is created to show the transitions between scenarios with respect to the controllable parameters. We apply our model to an experiment on mice with colon cancer and the drug Gemcitabine.

我们在能够代谢化疗药物的细菌存在的情况下，构建了化疗治疗癌症动力学的数学模型，从而破坏了治疗。我们研究了用抗生素药物补充癌症治疗的可能性，从而根除细菌或至少减轻它们对治疗前景的负面影响。我们的模型是一个由四个微分方程组成的非线性系统，我们对此进行了完整的分析，明确地描述了四种可能的结果，这取决于癌细胞或细菌是灭绝还是持续存在。通过比较原理的迭代应用证明了全局稳定性结果，并创建了分岔图来表示各场景之间相对于可控参数的转换。我们将我们的模型应用于结肠癌小鼠和药物吉西他滨的实验。

引用次数: 0

A mathematical study of anti-VEGF and cytotoxic therapies of cancer with optimal control 抗血管内皮生长因子和肿瘤细胞毒性治疗的数学研究。

IF 1.8 4区数学 Q2 BIOLOGY

Mathematical Biosciences

Pub Date : 2025-09-25 DOI: 10.1016/j.mbs.2025.109542

Shikun Li , Xiaoming Zheng , Ling Xue , Kun Zhao

This work studies two cancer treatments, anti-angiogenic therapy and chemotherapy, with a novel mathematical model and the associated optimal control problem. The model includes tumor cells, endothelial cells, immune cells, and Vascular Endothelial Growth Factor (VEGF), where the anti-angiogenic therapy only targets VEGF and the chemotherapy kills all cells indiscriminately. The optimal control problem minimizes the tumor burden and drug toxicity over a set of time-variant drug doses. The mathematical analysis shows the existence of the positive invariant set of the model over all the therapeutic strategies, the stability of multiple steady state solutions, as well as the existence and uniqueness of the optimal control solutions. The analysis and simulations lead to several significant findings. First, all the steady states with the vanished tumor are unstable under the anti-VEGF therapy, which confirms its limited efficacy as observed in clinics. Second, the Hopf bifurcation appears in each treatment approach with a common feature: the system exhibits periodic oscillations at low drug doses and transitions to a stable coexistence state at higher drug doses. Third, the optimal treatment strategy involves a delicate combination of both treatment types. This strategy is particularly effective when the anti-VEGF drug has a high binding affinity to VEGF molecules, and the chemotherapy drug has a small killing rate of immune cells and large killing rates of endothelial cells and tumor cells.

本文研究了抗血管生成治疗和化疗两种癌症治疗方法，并提出了一种新的数学模型和相关的最优控制问题。该模型包括肿瘤细胞、内皮细胞、免疫细胞和血管内皮生长因子（VEGF），其中抗血管生成治疗仅针对VEGF，化疗不分青红皂白地杀死所有细胞。最优控制问题使肿瘤负荷和药物毒性在一组时变药物剂量上最小化。数学分析证明了模型在所有治疗策略上的正不变集的存在性、多个稳态解的稳定性以及最优控制解的存在唯一性。分析和模拟得出了几个重要的发现。首先，在抗vegf治疗下，所有肿瘤消失的稳定状态都是不稳定的，这证实了其临床观察到的有限疗效。其次，Hopf分岔出现在每种治疗方法中都有一个共同的特征：系统在低药物剂量下表现出周期性振荡，在高药物剂量下过渡到稳定的共存状态。第三，最佳治疗策略涉及两种治疗类型的微妙结合。当抗VEGF药物与VEGF分子具有高结合亲和力，且化疗药物对免疫细胞杀伤率小，对内皮细胞和肿瘤细胞杀伤率大时，这种策略尤其有效。

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引用次数: 0

Nucleation feedback can drive establishment and maintenance of biased microtubule polarity in neurites 成核反馈可以驱动神经突中偏置微管极性的建立和维持。

IF 1.8 4区数学 Q2 BIOLOGY

Mathematical Biosciences

Pub Date : 2025-09-22 DOI: 10.1016/j.mbs.2025.109538

Hannah G. Scanlon , Gibarni Mahata , Anna C. Nelson , Scott A. McKinley , Melissa M. Rolls , Maria-Veronica Ciocanel

The microtubule cytoskeleton is comprised of dynamic, polarized filaments that facilitate transport within the cell. Polarized microtubule arrays are key to facilitating cargo transport in long cells such as neurons. Microtubules also undergo dynamic instability, where the plus and minus ends of the filaments switch between growth and shrinking phases, leading to frequent microtubule turnover. Although microtubules often completely disassemble and new filaments nucleate, microtubule arrays have been observed to both maintain their biased orientation throughout the cell lifetime and to rearrange their polarity as an adaptive response to injury. Motivated by cytoskeleton organization in neurites, we propose a spatially-explicit stochastic model of microtubule arrays and investigate how nucleation of new filaments could generate biased polarity in a simple linear domain. Using a continuous-time Markov chain model of microtubule growth dynamics, we model and parameterize two experimentally-validated nucleation mechanisms: nucleation feedback, where the direction of filament growth depends on existing microtubule content, and a checkpoint mechanism, where microtubules that nucleate in a direction opposite to the majority experience frequent catastrophe. When incorporating these validated mechanisms into the spatial model, we find that nucleation feedback is sufficient to establish biased polarity in neurites of different lengths, and that the emergence and maintenance of biased polarity is relatively stable in spite of stochastic fluctuations. This work provides a framework to study the relationship between microtubule nucleation and polarity, and could extend to give insights into mechanisms that drive the formation of polarized filament arrays in other biological settings.

微管细胞骨架由动态的极化细丝组成，促进细胞内的运输。极化微管阵列是促进长细胞（如神经元）中货物运输的关键。微管也经历动态不稳定性，其中细丝的正负端在生长和收缩阶段之间切换，导致频繁的微管周转。尽管微管经常完全解体，新的细丝形成核，但已经观察到微管阵列在整个细胞寿命中都保持其偏向性取向，并且作为对损伤的适应性反应重新排列其极性。在神经突细胞骨架组织的激励下，我们提出了一个空间明确的微管阵列随机模型，并研究了新细丝的成核如何在简单的线性域内产生偏极性。利用微管生长动力学的连续时间马尔可夫链模型，我们模拟并参数化了两种实验验证的成核机制：成核反馈机制，其中丝的生长方向取决于现有的微管含量；以及检查点机制，其中与大多数方向相反的微管经常发生突变。当将这些验证的机制纳入空间模型时，我们发现成核反馈足以在不同长度的神经突中建立偏极性，并且尽管有随机波动，偏极性的出现和维持是相对稳定的。这项工作为研究微管成核和极性之间的关系提供了一个框架，并可以扩展到深入了解在其他生物环境中驱动极化灯丝阵列形成的机制。

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引用次数: 0

A dynamic model for Waddington’s landscape accounting for cell-to-cell communication 沃丁顿景观的动态模型，用于解释细胞间的通信。

IF 1.8 4区数学 Q2 BIOLOGY

Mathematical Biosciences

Pub Date : 2025-09-19 DOI: 10.1016/j.mbs.2025.109537

Simon Merkt , Lara Fuhrmann , Erika Dudkin , Andreas Schlitzer , Barbara Niethammer , Jan Hasenauer

Waddington’s landscape provides a conceptual model for developmental processes. It is the basis of various mathematical models describing cell maturation and development at cell and population levels. Yet, these mathematical models mostly disregard cell-to-cell communication, an essential process that modulates cellular decision-making and population dynamics.

In this study, we provide a dynamical model for cell maturation and development which can be seen as an extension of Waddington’s landscape. The coupled system of partial and ordinary differential equations describes cell density along the cell state together with ligand concentrations. Cell-state-dependent ligand production determines ligand availability, which controls population-level processes. We provide proof of the existence and uniqueness of solutions for our coupled differential equation system and demonstrate the model’s validity by analyzing single-cell transcriptomics data. Our results show that cell-to-cell communication is essential for accurately depicting biological recovery processes, such as the regeneration of stem cells in the intestine’s crypt and the response of immune cells upon LSP stimulation.

Our findings underscore the importance of incorporating cell-to-cell communication into mathematical models of biological development. By doing so, we unlock the potential for deeper insights into complex processes such as tissue regeneration and immune responses, offering new avenues for understanding and predicting the dynamics of biological recovery and cell activation.

沃丁顿的景观为发展过程提供了一个概念模型。它是在细胞和群体水平上描述细胞成熟和发育的各种数学模型的基础。然而，这些数学模型大多忽略了细胞间的通信，这是调节细胞决策和种群动态的基本过程。在这项研究中，我们提供了一个细胞成熟和发育的动态模型，可以看作是沃丁顿景观的延伸。偏微分方程和常微分方程的耦合系统描述了沿着细胞状态的细胞密度和配体浓度。细胞状态依赖性配体的产生决定了配体的可用性，从而控制了种群水平的过程。通过对单细胞转录组学数据的分析，证明了该耦合微分方程组解的存在性和唯一性，并证明了该模型的有效性。我们的研究结果表明，细胞间通信对于准确描述生物恢复过程至关重要，例如肠隐窝中干细胞的再生和免疫细胞对LSP刺激的反应。我们的发现强调了将细胞间通讯纳入生物发育数学模型的重要性。通过这样做，我们解锁了深入了解组织再生和免疫反应等复杂过程的潜力，为理解和预测生物恢复和细胞激活的动力学提供了新的途径。

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引用次数: 0

Turing patterns in a morphogenetic model with single regulatory function 具有单一调控功能的形态发生模型中的图灵模式。

IF 1.8 4区数学 Q2 BIOLOGY

Mathematical Biosciences

Pub Date : 2025-09-17 DOI: 10.1016/j.mbs.2025.109536

Mohamed Amine Ouchdiri , Saad Benjelloun , Adnane Saoud , Irene Otero-Muras

Confirming Turing’s theory of morphogens in developmental processes is challenging, and synthetic biology has opened new avenues for testing Turing’s predictions. Synthetic mammalian pattern formation has been recently achieved through a reaction–diffusion system based on the short-range activator (Nodal) and the long-range inhibitor (Lefty) topology, where a single function regulates both morphogens. In this paper, we investigate the emergence of Turing patterns in the synthetic Nodal-Lefty system. First, we prove the existence of a global solution and derive conditions for Turing instability through linear stability analysis. Subsequently, we examine the behavior of the system near the bifurcation threshold, employing weakly nonlinear analysis, and using multiple time scales, we derive the amplitude equations for supercritical and subcritical cases. The results demonstrate the ability of the system to support various patterns, with the subcritical Turing instability playing a crucial role in the formation of dissipative structures observed experimentally.

证实图灵关于发育过程中形态因子的理论是具有挑战性的，而合成生物学为测试图灵的预测开辟了新的途径。最近，通过一种基于短程激活剂（Nodal）和远程抑制剂（Lefty）拓扑结构的反应扩散系统，合成哺乳动物的模式形成已经实现，其中一个功能调节两个形态因子。在本文中，我们研究了图灵模式在合成左节点系统中的出现。首先，通过线性稳定性分析，证明了全局解的存在性，并导出了图灵不稳定性的条件。随后，我们研究了系统在分岔阈值附近的行为，采用弱非线性分析，并使用多时间尺度，我们推导了超临界和亚临界情况下的振幅方程。结果表明，该系统具有支持多种模式的能力，亚临界图灵不稳定性在实验观察到的耗散结构的形成中起着至关重要的作用。

引用次数: 0

Modeling bistable dynamics arising from macrophage–tumor interactions in the tumor microenvironment 模拟肿瘤微环境中巨噬细胞-肿瘤相互作用引起的双稳态动力学。

IF 1.8 4区数学 Q2 BIOLOGY

Mathematical Biosciences

Pub Date : 2025-09-16 DOI: 10.1016/j.mbs.2025.109534

Hwayeon Ryu , Susanna Röblitz , Kamila Larripa , Anna-Simone Frank

Macrophages in the tumor microenvironment (TME), known as tumor-associated macrophages (TAMs), originate primarily from circulating monocytes that differentiate under the influence of tumor-derived signals. Within the TME, naïve macrophages can adopt either a pro-inflammatory, anti-tumor (M1-like) or anti-inflammatory, pro-tumor (M2-like) phenotype. These phenotypic shifts significantly affect tumor progression, making TAMs attractive targets for therapeutic intervention aimed at blocking recruitment, promoting anti-tumor polarization, or disrupting tumor–macrophage interactions. In this study, we develop a mathematical model capturing the temporal dynamics of tumor volume alongside populations of naïve, M1-like, M2-like, and mixed (M1/M2) phenotype TAMs. The model incorporates the bidirectional influence between tumor development and macrophage polarization. Through numerical simulations with different parameter sets, our tumor–macrophage population model exhibits the emergence of bistability, demonstrating the system becomes more controllable, responsive to perturbations, and sensitive to immunotherapy. We conduct the bifurcation as well as global sensitivity analyses to identify regions of bistability for tumor dynamics in the parameter space and the impact of sensitive parameters on TME. These results are then linked to treatment strategies that may effectively induce transitions from high to low tumor burden.

肿瘤微环境（TME）中的巨噬细胞，称为肿瘤相关巨噬细胞（tam），主要来自循环单核细胞，在肿瘤来源信号的影响下分化。在TME内，naïve巨噬细胞可以采用促炎、抗肿瘤（m1样）或抗炎、促肿瘤（m2样）表型。这些表型变化显著影响肿瘤进展，使tam成为旨在阻断招募、促进抗肿瘤极化或破坏肿瘤-巨噬细胞相互作用的治疗干预的有吸引力的靶点。在这项研究中，我们建立了一个数学模型，捕捉肿瘤体积的时间动态以及naïve， M1样，M2样和混合（M1/M2）表型tam的种群。该模型纳入了肿瘤发展与巨噬细胞极化之间的双向影响。通过不同参数集的数值模拟，我们的肿瘤-巨噬细胞群体模型显示出双稳定性的出现，表明系统变得更加可控，对扰动反应灵敏，对免疫治疗敏感。我们进行了分岔分析和全局敏感性分析，以确定参数空间中肿瘤动力学的双稳定区域以及敏感参数对TME的影响。这些结果与可能有效诱导从高肿瘤负荷到低肿瘤负荷转变的治疗策略相关联。

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引用次数: 0

CAR T-cell and oncolytic virus dynamics and determinants of combination therapy success for glioblastoma CAR - t细胞和溶瘤病毒动力学和胶质母细胞瘤联合治疗成功的决定因素。

IF 1.8 4区数学 Q2 BIOLOGY

Mathematical Biosciences

Pub Date : 2025-09-15 DOI: 10.1016/j.mbs.2025.109531

Martina Conte , Agata Xella , Ryan T. Woodall , Kevin A. Cassady , Sergio Branciamore , Christine E. Brown , Russell C. Rockne

Glioblastoma is a highly aggressive and treatment-resistant primary brain cancer. While chimeric antigen receptor (CAR) T-cell therapy has demonstrated promising results in targeting these tumors, it has not yet been curative. An innovative approach to improve CAR T-cell efficacy is to combine them with other immune modulating therapies. In this study, we investigate in vitro combination of IL-13R

α

2 targeted CAR T-cells with an oncolytic virus (OV) and study the complex interplay between tumor cells, CAR T-cells, and OV dynamics with a novel mathematical model. We fit the model to data collected from experiments with each therapy individually and in combination to reveal determinants of therapy synergy and improved efficacy. Our analysis reveals that the virus bursting size is a critical parameter in determining the net tumor infection rate and overall combination treatment efficacy. Moreover, the model predicts that administering the oncolytic virus simultaneously with, or prior to, CAR T-cells could maximize therapeutic efficacy.

胶质母细胞瘤是一种高度侵袭性和治疗抵抗性的原发性脑癌。虽然嵌合抗原受体（CAR） t细胞疗法在靶向这些肿瘤方面已经显示出有希望的结果，但它尚未治愈。提高CAR - t细胞疗效的一种创新方法是将它们与其他免疫调节疗法相结合。在这项研究中，我们研究了IL-13Rα2靶向CAR - t细胞与溶瘤病毒（OV）的体外联合，并通过一个新的数学模型研究了肿瘤细胞、CAR - t细胞和OV动力学之间的复杂相互作用。我们将模型拟合到从每种治疗单独和组合的实验中收集的数据中，以揭示治疗协同作用和改善疗效的决定因素。我们的分析表明，病毒破裂大小是决定净肿瘤感染率和综合治疗效果的关键参数。此外，该模型预测，溶瘤病毒与CAR - t细胞同时或先于CAR - t细胞使用可以最大限度地提高治疗效果。

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引用次数: 0