优化疫苗诱导免疫治疗黑素瘤的疗效。

IF 2 4区 数学 Q2 BIOLOGY
Ibrahim Chamseddine, Manoj Kambara, Priya Bhatt, Shari Pilon-Thomas, Katarzyna A Rejniak
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引用次数: 0

摘要

癌症治疗疫苗是通过放大现有的免疫反应来增强患者自身的免疫系统。基于细菌的emm55疫苗与PD1检查点抑制剂的局部注射对B16黑色素瘤小鼠模型产生了很强的抗肿瘤作用。然而,为联合治疗设计最佳注射顺序和频率并非易事。在此,我们建立了一个与实验数据校准的耦合常微分方程模型,并使用网格自适应直接搜索方法来优化emm55疫苗和抗pd1联合治疗的治疗方案。本方法确定早期连续注射疫苗联合分散注射抗pd1分离时间越短,肿瘤缩小效果越好。优化方案导致单独疫苗治疗的肿瘤面积减少两倍,联合治疗的肿瘤面积减少四倍。我们的研究结果揭示了肿瘤亚群在最佳治疗条件下的动态,为有效的治疗设计确定了路径。类似的计算框架可以应用于其他肿瘤和其他联合疗法,以在相当不受限制和廉价的环境中产生实验可测试的假设。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Optimizing the Efficacy of Vaccine-Induced Immunotherapy in Melanomas.

Cancer therapeutic vaccines are used to strengthen a patient's own immune system by amplifying existing immune responses. Intralesional administration of the bacteria-based emm55 vaccine together with the PD1 checkpoint inhibitor produced a strong anti-tumor effect against the B16 melanoma murine model. However, it is not trivial to design an optimal order and frequency of injections for combination therapies. Here, we developed a coupled ordinary differential equations model calibrated to experimental data and used the mesh adaptive direct search method to optimize the treatment protocols of the emm55 vaccine and anti-PD1 combined therapy. This method determined that early consecutive vaccine injections combined with distributed anti-PD1 injections of decreasing separation time yielded the best tumor size reduction. The optimized protocols led to a twofold decrease in tumor area for the vaccine-alone treatment, and a fourfold decrease for the combined therapy. Our results reveal the tumor subpopulation dynamics in the optimal treatment condition, defining the path for efficacious treatment design. Similar computational frameworks can be applied to other tumors and other combination therapies to generate experimentally testable hypotheses in a fairly unrestricted and inexpensive setting.

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来源期刊
CiteScore
3.90
自引率
8.60%
发文量
123
审稿时长
7.5 months
期刊介绍: The Bulletin of Mathematical Biology, the official journal of the Society for Mathematical Biology, disseminates original research findings and other information relevant to the interface of biology and the mathematical sciences. Contributions should have relevance to both fields. In order to accommodate the broad scope of new developments, the journal accepts a variety of contributions, including: Original research articles focused on new biological insights gained with the help of tools from the mathematical sciences or new mathematical tools and methods with demonstrated applicability to biological investigations Research in mathematical biology education Reviews Commentaries Perspectives, and contributions that discuss issues important to the profession All contributions are peer-reviewed.
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