Shelby Wilson
INRIA Rhone-Alpes
Objectives: We highlight how immunotherapy might be used to overcome the effects of two immuno-regulatory agents exploited by cancer: regulatory T cells and the Transforming Growth Factor (TGF)-beta protein. Using experimental data, we develop a mathematical model to gain insight into the cooperative interaction between anti-TGF-beta and vaccine treatments.
Methods: We develop a model consisting of ordinary differential equations that follows the dynamics of the tumor size, TGF-beta concentration, activated cytotoxic effector cells, and regulatory T cells. Nonlinear least squares is used to fit model parameters to experimental data. Using numerical simulations and stability analysis, we study the following scenarios: a control case of no treatment, anti-TGF-beta treatment, vaccine treatment, and combined anti-TGF-beta vaccine treatments.
Results: Consistent with experimental data, we show that monotherapy alone cannot successfully eradicate a tumor and conclude that tumor eradication requires the combination of these therapeutic approaches.
Conclusions: We demonstrate that our model captures the observed experimental results, and hence can be potentially used in designing future experiments involving this approach to immunotherapy.
References:
[1] D. Kirschner, T. Jackson, and J. Arciero. A mathematical model of tumor- immune evasion and siRNA treatment. Discrete and Continuous Dynamical Systems – Series B, 4(1):39–58, Nov. 2003.
[2] Y. Kogan, U. Forys, O. Shukron, N. Kronik, and Z. Agur. Cellular immunotherapy for high grade gliomas: Mathematical analysis deriving efficacious infusion rates based on patient requirements. SIAM Journal on Applied Mathematics, 70(6):1953–1976, 2010.
[3] M. Terabe, E. Ambrosino, S. Takaku, J. J. O’Konek, D. Venzon, S. Lonning, J. P. McPherson, and J. A. Berzofsky. Synergistic enhancement of CD8+ T cell-mediated tumor vaccine efficacy by an antitransforming growth factor-beta monoclonal antibody. Clinical Cancer Research, 15(21):6560–9, 2009.
[4] S. Wilson and D. Levy. A mathematical model of the enhancement of tumor vaccine efficacy by immunotherapy. Bulletin of Mathematical Biology, (accepted).
Reference: PAGE 21 () Abstr 2549 [www.page-meeting.org/?abstract=2549]
Poster: Oncology