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用于最佳控制小鼠模型的树突状细胞免疫疗法改进

Dendritic Immunotherapy Improvement for an Optimal Control Murine Model.

作者信息

Rangel-Reyes J C, Chimal-Eguía J C, Castillo-Montiel E

机构信息

Laboratorio de Simulación y Modelado, Centro de Investigación en Computación, Instituto Politécnico Nacional, Av. Juan de Dios Bátiz, Esq. Miguel Othón de Mendizábal, Col. Nueva Industrial Vallejo Delegación Gustavo A. Madero, 07738 Ciudad de México, Mexico.

出版信息

Comput Math Methods Med. 2017;2017:5291823. doi: 10.1155/2017/5291823. Epub 2017 Aug 20.

Abstract

Therapeutic protocols in immunotherapy are usually proposed following the intuition and experience of the therapist. In order to deduce such protocols mathematical modeling, optimal control and simulations are used instead of the therapist's experience. Clinical efficacy of dendritic cell (DC) vaccines to cancer treatment is still unclear, since dendritic cells face several obstacles in the host environment, such as immunosuppression and poor transference to the lymph nodes reducing the vaccine effect. In view of that, we have created a mathematical murine model to measure the effects of dendritic cell injections admitting such obstacles. In addition, the model considers a therapy given by bolus injections of small duration as opposed to a continual dose. Doses timing defines the therapeutic protocols, which in turn are improved to minimize the tumor mass by an optimal control algorithm. We intend to supplement therapist's experience and intuition in the protocol's implementation. Experimental results made on mice infected with melanoma with and without therapy agree with the model. It is shown that the dendritic cells' percentage that manages to reach the lymph nodes has a crucial impact on the therapy outcome. This suggests that efforts in finding better methods to deliver DC vaccines should be pursued.

摘要

免疫疗法中的治疗方案通常是根据治疗师的直觉和经验提出的。为了推导此类方案,采用了数学建模、最优控制和模拟,而非治疗师的经验。树突状细胞(DC)疫苗对癌症治疗的临床疗效仍不明确,因为树突状细胞在宿主环境中面临多种障碍,如免疫抑制以及向淋巴结的转运不佳,从而降低了疫苗效果。鉴于此,我们创建了一个数学小鼠模型来衡量考虑到这些障碍的树突状细胞注射效果。此外,该模型考虑的是短时间推注给药,而非持续给药。给药时间定义了治疗方案,进而通过最优控制算法对其进行改进,以将肿瘤体积最小化。我们旨在补充治疗师在方案实施中的经验和直觉。对感染黑色素瘤且接受或未接受治疗的小鼠进行的实验结果与该模型相符。结果表明,成功抵达淋巴结的树突状细胞百分比对治疗结果具有关键影响。这表明应致力于寻找更好的方法来递送DC疫苗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cda/5585610/0b934ed5f9e6/CMMM2017-5291823.001.jpg

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