Department of Mathematics and Computer Science, University of Catania, V,le A, Doria 6, Catania, Italy.
BMC Bioinformatics. 2010 Oct 15;11 Suppl 7(Suppl 7):S13. doi: 10.1186/1471-2105-11-S7-S13.
The Triplex cell vaccine is a cancer cellular vaccine that can prevent almost completely the mammary tumor onset in HER-2/neu transgenic mice. In a translational perspective, the activity of the Triplex vaccine was also investigated against lung metastases showing that the vaccine is an effective treatment also for the cure of metastases. A future human application of the Triplex vaccine should take into account several aspects of biological behavior of the involved entities to improve the efficacy of therapeutic treatment and to try to predict, for example, the outcomes of longer experiments in order to move faster towards clinical phase I trials. To help to address this problem, MetastaSim, a hybrid Agent Based - ODE model for the simulation of the vaccine-elicited immune system response against lung metastases in mice is presented. The model is used as in silico wet-lab. As a first application MetastaSim is used to find protocols capable of maximizing the total number of prevented metastases, minimizing the number of vaccine administrations.
The model shows that it is possible to obtain "in silico" a 45% reduction in the number of vaccinations. The analysis of the results further suggests that any optimal protocol for preventing lung metastases formation should be composed by an initial massive vaccine dosage followed by few vaccine recalls.
Such a reduction may represent an important result from the point of view of translational medicine to humans, since a downsizing of the number of vaccinations is usually advisable in order to minimize undesirable effects. The suggested vaccination strategy also represents a notable outcome. Even if this strategy is commonly used for many infectious diseases such as tetanus and hepatitis-B, it can be in fact considered as a relevant result in the field of cancer-vaccines immunotherapy. These results can be then used and verified in future "in vivo" experiments, and their outcome can be used to further improve and refine the model.
Triplex 细胞疫苗是一种癌症细胞疫苗，几乎可以完全预防 HER-2/neu 转基因小鼠的乳腺肿瘤发生。从转化医学的角度来看，还研究了 Triplex 疫苗对肺转移的作用，结果表明该疫苗也是治疗转移的有效方法。Triplex 疫苗在人类中的未来应用应考虑到所涉及实体的几个生物学行为方面，以提高治疗效果，并尝试预测例如，更长时间实验的结果，以便更快地进入 I 期临床试验。为了帮助解决这个问题，提出了一种用于模拟疫苗诱导的免疫系统对小鼠肺转移反应的混合基于代理的 ODE 模型 MetastaSim。该模型用作计算机湿实验室。作为第一个应用，MetastaSim 用于找到能够最大限度地减少疫苗接种次数、预防转移数量的方案。
模型表明，有可能在“计算机”中减少 45%的疫苗接种次数。结果分析进一步表明，任何预防肺转移形成的最佳方案都应由初始大量疫苗剂量组成，然后是几次疫苗召回。
从转化医学的角度来看，这种减少可能是一个重要的结果，因为为了最小化不良反应，通常建议减少疫苗接种次数。建议的接种策略也是一个值得注意的结果。即使这种策略通常用于许多传染病，如破伤风和乙型肝炎，它实际上也可以被认为是癌症疫苗免疫治疗领域的一个重要结果。这些结果可以在未来的“体内”实验中使用和验证，并可以用于进一步改进和完善模型。
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