Coletti Roberta, Pugliese Andrea, Marchetti Luca
University of Trento, Department of mathematics, Trento 38123, Italy; Fondazione The Microsoft Research - University of Trento Centre for Computational and Systems Biology, Rovereto 38068, Italy.
University of Trento, Department of mathematics, Trento 38123, Italy.
J Theor Biol. 2021 Jan 21;509:110500. doi: 10.1016/j.jtbi.2020.110500. Epub 2020 Sep 24.
In this paper we analyze the potential effect of immunotherapies on castration-resistant form of human Prostate Cancer (PCa). In particular, we examine the potential effect of the dendritic vaccine sipuleucel-T, the only currently available immunotherapy option for advanced PCa, and of ipilimumab, a drug targeting the Cytotoxic T-Lymphocyte Antigen 4 (CTLA4), exposed on the CTLs membrane, currently under Phase II clinical trial. The model, building on the one by Rutter and Kuang, includes different types of immune cells and interactions and is parameterized on available data. Our results show that the vaccine has only a very limited effect on PCa, while repeated treatments with ipilimumab appear potentially capable of controlling and even eradicating an androgen-independent prostate cancer. From a mathematical analysis of a simplified model, it seems likely that, under continuous administration of ipilimumab, the system lies in a bistable situation where both the no-tumor equilibrium and the high-tumor equilibrium are attractive. The schedule of periodic treatments could then determine the outcome, and mathematical models could help determine an optimal schedule.
在本文中，我们分析了免疫疗法对去势抵抗性人类前列腺癌（PCa）的潜在影响。具体而言，我们研究了树突状细胞疫苗西妥昔单抗（sipuleucel-T）以及伊匹单抗（ipilimumab）的潜在影响，前者是目前唯一可用于晚期PCa的免疫疗法，后者是一种靶向细胞毒性T淋巴细胞抗原4（CTLA4）的药物，该抗原暴露于CTL细胞膜上，目前正处于II期临床试验阶段。该模型基于Rutter和Kuang的模型构建，包含不同类型的免疫细胞及其相互作用，并根据现有数据进行参数化。我们的结果表明，该疫苗对PCa的影响非常有限，而反复使用伊匹单抗进行治疗似乎有可能控制甚至根除雄激素非依赖性前列腺癌。通过对一个简化模型的数学分析，似乎在持续给予伊匹单抗的情况下，系统处于双稳态，无肿瘤平衡态和高肿瘤平衡态都是吸引子。那么定期治疗的方案可以决定结果，数学模型可以帮助确定最佳方案。
