Jarrett2018 - trastuzumab-induced immune response in murine HER2+ breast cancer model

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Short description
The paper describes a model on the trastuzumab-induced immune response in murine(mouse) HER2+ breast cancer.
Created by COPASI 4.25 (Build 207) 

This model is described in the article: Mathematical modelling of trastuzumab-induced immune response in an in vivo murine model of HER2+ breast cancer 
Angela M. Jarrett, Meghan J. Bloom, Wesley Godfrey, Anum K. Syed, David A. Ekrut, Lauren I. Ehrlich, Thomas E. Yankeelov, Anna G. Sorace 
Mathematical Medicine and Biology: A Journal of the IMA (2018) 00, 1–30 

Abstract: 
The goal of this study is to develop an integrated, mathematical–experimental approach for understanding the interactions between the immune system and the effects of trastuzumab on breast cancer that overexpresses the human epidermal growth factor receptor 2 (HER2+). A system of coupled, ordinary differential equations was constructed to describe the temporal changes in tumour growth, along with intratumoural changes in the immune response, vascularity, necrosis and hypoxia. The mathematical model is calibrated with serially acquired experimental data of tumour volume, vascularity, necrosis and hypoxia obtained from either imaging or histology from a murine model of HER2+ breast cancer. Sensitivity analysis shows that model components are sensitive for 12 of 13 parameters, but accounting for uncertainty in the parameter values, model simulations still agree with the experimental data. Given theinitial conditions, the mathematical model predicts an increase in the immune infiltrates over time in the treated animals. Immunofluorescent staining results are presented that validate this prediction by showing an increased co-staining of CD11c and F4/80 (proteins expressed by dendritic cells and/or macrophages) in the total tissue for the treated tumours compared to the controls. We posit that the proposed mathematical–experimental approach can be used to elucidate driving interactions between the trastuzumab-induced responses in the tumour and the immune system that drive the stabilization of vasculature while simultaneously decreasing tumour growth—conclusions revealed by the mathematical model that were not deducible from the experimental data alone. 

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Format
SBML (L3V1)
Related Publication
  • Mathematical modelling of trastuzumab-induced immune response in an in vivo murine model of HER2+ breast cancer
  • Angela M. Jarrett, Meghan J. Bloom, Wesley Godfrey, Anum K. Syed, David A. Ekrut, Lauren I. Ehrlich, Thomas E. Yankeelov, Anna G. Sorace
  • Mathematical Medicine and Biology: A Journal of the IMA , 8/ 2018 , Issue 00 , pages: 1-30
  • Correspondence: Anna G. Sorace E-mail address: anna.sorace@austin.utexas.edu Department of Biomedical Engineering; Department of Diagnostic Medicine, Department of Oncology, and Livestrong Cancer Institutes at The University of Texas at Austin, Austin, TX 78712, USA
  • The goal of this study is to develop an integrated, mathematical–experimental approach for understanding the interactions between the immune system and the effects of trastuzumab on breast cancer that overexpresses the human epidermal growth factor receptor 2 (HER2+). A system of coupled, ordinary differential equations was constructed to describe the temporal changes in tumour growth, along with intratumoural changes in the immune response, vascularity, necrosis and hypoxia. The mathematical model is calibrated with serially acquired experimental data of tumour volume, vascularity, necrosis and hypoxia obtained from either imaging or histology from a murine model of HER2+ breast cancer. Sensitivity analysis shows that model components are sensitive for 12 of 13 parameters, but accounting for uncertainty in the parameter values, model simulations still agree with the experimental data. Given theinitial conditions, the mathematical model predicts an increase in the immune infiltrates over time in the treated animals. Immunofluorescent staining results are presented that validate this prediction by showing an increased co-staining of CD11c and F4/80 (proteins expressed by dendritic cells and/or macrophages) in the total tissue for the treated tumours compared to the controls. We posit that the proposed mathematical–experimental approach can be used to elucidate driving interactions between the trastuzumab-induced responses in the tumour and the immune system that drive the stabilization of vasculature while simultaneously decreasing tumour growth—conclusions revealed by the mathematical model that were not deducible from the experimental data alone.
Contributors
Jinghao Men

Metadata information

hasTaxon
Taxonomy Mus musculus
isVersionOf
hasProperty
Mathematical Modelling Ontology Ordinary differential equation model
0000305
isDescribedBy
occursIn
Brenda Tissue Ontology breast

Curation status
Curated


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Model files

Jarrett2018.xml SBML L2V4 representation of trastuzumab-induced immune response in an in vivo murine model of HER2+ breast cancer model--control group 75.05 KB Preview | Download

Additional files

Jarrett2018.cps CPS file of the model in COPASI 97.69 KB Preview | Download
Jarrett2018.sedml Auto-generated SEDML file 1.14 KB Preview | Download

  • Model originally submitted by : Jinghao Men
  • Submitted: 05-Jul-2019 11:15:11
  • Last Modified: 10-Jul-2019 11:54:37
Revisions
  • Version: 9 public model Download this version
    • Submitted on: 10-Jul-2019 11:54:37
    • Submitted by: Jinghao Men
    • With comment: Automatically added model identifier BIOMD0000000745
  • Version: 3 public model Download this version
    • Submitted on: 05-Jul-2019 11:15:11
    • Submitted by: Jinghao Men
    • With comment: Edited model metadata online.
Curator's comment:
(added: 08 Jul 2019, 15:31:04, updated: 08 Jul 2019, 15:31:04)
Publication figure 5A reproduced as per literature. Figure 5B (tumour size) can also be reproduced. Figure 5C/D can be reproduced if changed to another set of parameters given. Figure data is generated using COPASI 4.25 (build 197).