A mathematical model of the enhancement of tumor vaccine efficacy by immunotherapy

Bull Math Biol. 2012 Jul;74(7):1485-500. doi: 10.1007/s11538-012-9722-4. Epub 2012 Mar 22.

Abstract

TGF-β is an immunoregulatory protein that contributes to inadequate antitumor immune responses in cancer patients. Recent experimental data suggests that TGF-β inhibition alone, provides few clinical benefits, yet it can significantly amplify the anti-tumor immune response when combined with a tumor vaccine. We develop a mathematical model in order to gain insight into the cooperative interaction between anti-TGF-β and vaccine treatments. The mathematical model follows the dynamics of the tumor size, TGF-β concentration, activated cytotoxic effector cells, and regulatory T cells. Using numerical simulations and stability analysis, we study the following scenarios: a control case of no treatment, anti-TGF-β treatment, vaccine treatment, and combined anti-TGF-β vaccine treatments. We show that our model is capable of capturing the observed experimental results, and hence can be potentially used in designing future experiments involving this approach to immunotherapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cancer Vaccines / immunology
  • Cancer Vaccines / therapeutic use*
  • Computer Simulation
  • Dendritic Cells / immunology
  • Humans
  • Immunotherapy*
  • Mice
  • Models, Biological*
  • Neoplasms / therapy*
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Regulatory / immunology
  • Transforming Growth Factor beta / antagonists & inhibitors*
  • Transforming Growth Factor beta / immunology

Substances

  • Cancer Vaccines
  • Transforming Growth Factor beta