Institute for Physiology, Charité Universitätsmedizin Berlin, Berlin, Germany.
PLoS One. 2011;6(8):e23257. doi: 10.1371/journal.pone.0023257. Epub 2011 Aug 17.
Peptide vaccination in cancer therapy is a promising alternative to conventional methods. However, the parameters for this personalized treatment are difficult to access experimentally. In this respect, in silico models can help to narrow down the parameter space or to explain certain phenomena at a systems level. Herein, we develop two empirical interaction potentials specific to B-cell and T-cell receptor complexes and validate their applicability in comparison to a more general potential. The interaction potentials are applied to the model VaccImm which simulates the immune response against solid tumors under peptide vaccination therapy. This multi-agent system is derived from another immune system simulator (C-ImmSim) and now includes a module that enables the amino acid sequence of immune receptors and their ligands to be taken into account. The multi-agent approach is combined with approved methods for prediction of major histocompatibility complex (MHC)-binding peptides and the newly developed interaction potentials. In the analysis, we critically assess the impact of the different modules on the simulation with VaccImm and how they influence each other. In addition, we explore the reasons for failures in inducing an immune response by examining the activation states of the immune cell populations in detail.In summary, the present work introduces immune-specific interaction potentials and their application to the agent-based model VaccImm which simulates peptide vaccination in cancer therapy.
肽疫苗接种在癌症治疗中是一种有前途的替代传统方法。然而,这种个性化治疗的参数很难通过实验获得。在这方面,计算模型可以帮助缩小参数空间或从系统层面解释某些现象。在此,我们开发了两种针对 B 细胞和 T 细胞受体复合物的经验相互作用势,并将其与更通用的势进行比较,验证其适用性。将相互作用势应用于模型 VaccImm,该模型模拟了肽疫苗接种治疗下针对实体瘤的免疫反应。该多代理系统源自另一个免疫系统模拟器(C-ImmSim),现在包括一个模块,该模块能够考虑免疫受体及其配体的氨基酸序列。多代理方法与预测主要组织相容性复合物(MHC)结合肽的已批准方法和新开发的相互作用势相结合。在分析中,我们批判性地评估了 VaccImm 中不同模块对模拟的影响以及它们如何相互影响。此外,我们通过详细检查免疫细胞群体的激活状态来探讨诱导免疫反应失败的原因。总之,本工作介绍了免疫特异性相互作用势及其在基于代理的模型 VaccImm 中的应用,该模型模拟了癌症治疗中的肽疫苗接种。