A mathematical model to elucidate brain tumor abrogation by immunotherapy with T11 target structure

PLoS One. 2015 May 8;10(5):e0123611. doi: 10.1371/journal.pone.0123611. eCollection 2015.

Abstract

T11 Target structure (T11TS), a membrane glycoprotein isolated from sheep erythrocytes, reverses the immune suppressed state of brain tumor induced animals by boosting the functional status of the immune cells. This study aims at aiding in the design of more efficacious brain tumor therapies with T11 target structure. We propose a mathematical model for brain tumor (glioma) and the immune system interactions, which aims in designing efficacious brain tumor therapy. The model encompasses considerations of the interactive dynamics of glioma cells, macrophages, cytotoxic T-lymphocytes (CD8(+) T-cells), TGF-β, IFN-γ and the T11TS. The system undergoes sensitivity analysis, that determines which state variables are sensitive to the given parameters and the parameters are estimated from the published data. Computer simulations were used for model verification and validation, which highlight the importance of T11 target structure in brain tumor therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Brain Neoplasms / immunology*
  • Brain Neoplasms / pathology
  • Brain Neoplasms / therapy*
  • CD8-Positive T-Lymphocytes / immunology
  • Female
  • Glioma / immunology
  • Glioma / pathology
  • Glioma / therapy
  • Humans
  • Immunotherapy*
  • Interferon-gamma / pharmacology
  • Least-Squares Analysis
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Male
  • Membrane Glycoproteins / administration & dosage
  • Membrane Glycoproteins / immunology*
  • Models, Biological*
  • Numerical Analysis, Computer-Assisted
  • Rats
  • Sheep
  • Transforming Growth Factor beta / pharmacology

Substances

  • Membrane Glycoproteins
  • Transforming Growth Factor beta
  • Interferon-gamma

Grants and funding

This work is financially supported by Department of Science and Technology (DST) India (grant no. SR/S4/MS:627/09-1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.