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Mathematical modelling of cancer stem cell-targeted immunotherapy.

Authors
  • Sigal, Daniel1
  • Przedborski, Michelle2
  • Sivaloganathan, Darshan3
  • Kohandel, Mohammad4
  • 1 Schulich School of Medicine and Dentistry, University of Western Ontario, ON N6A 3K7 Canada. , (Canada)
  • 2 Department of Applied Mathematics, University of Waterloo, ON N2L 3G1.
  • 3 Lewis-Sigler Institute for Integrative Genomics, Princeton University, NJ 08544 Canada. , (Canada)
  • 4 Department of Applied Mathematics, University of Waterloo, ON N2L 3G1. Electronic address: [email protected]
Type
Published Article
Journal
Mathematical biosciences
Publication Date
Oct 14, 2019
Volume
318
Pages
108269–108269
Identifiers
DOI: 10.1016/j.mbs.2019.108269
PMID: 31622595
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

The cancer stem cell hypothesis states that tumors are heterogeneous and comprised of several different cell types that have a range of reproductive potentials. Cancer stem cells (CSCs), represent one class of cells that has both reproductive potential and the ability to differentiate. These cells are thought to drive the progression of aggressive and recurring cancers since they give rise to all other constituent cells within a tumor. With the development of immunotherapy in the last decade, the specific targeting of CSCs has become feasible and presents a novel therapeutic approach. In this paper, we construct a mathematical model to study how specific components of the immune system, namely dendritic cells and cytotoxic T-cells interact with different cancer cell types (CSCs and non-CSCs). Using a system of ordinary differential equations, we model the effects of immunotherapy, specifically dendritic cell vaccines and T-cell adoptive therapy, on tumor growth, with and without chemotherapy. The model reproduces several results observed in the literature, including temporal measurements of tumor size from in vivo experiments, and it is used to predict the optimal treatment schedule when combining different treatment modalities. Importantly, the model also demonstrates that chemotherapy increases tumorigenicity whereas CSC-targeted immunotherapy decreases it. Copyright © 2019 Elsevier Inc. All rights reserved.

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