The role of TNF-α inhibitor in glioma virotherapy: A mathematical model

  • Received: 22 June 2016 Accepted: 30 June 2016 Published: 01 January 2017
  • MSC : Primary: 92C42, 92C50; Secondary: 49J15

  • Virotherapy, using herpes simplex virus, represents a promising therapy of glioma. But the innate immune response, which includes TNF-α produced by macrophages, reduces the effectiveness of the treatment. Hence treatment with TNF-α inhibitor may increase the effectiveness of the virotherapy. In the present paper we develop a mathematical model that includes continuous infusion of the virus in combination with TNF-α inhibitor. We study the efficacy of the treatment under different combinations of the two drugs for different scenarios of the burst size of newly formed virus emerging from dying infected cancer cells. The model may serve as a first step toward developing an optimal strategy for the treatment of glioma by the combination of TNF-α inhibitor and oncolytic virus injection.

    Citation: Elzbieta Ratajczyk, Urszula Ledzewicz, Maciej Leszczynski, Avner Friedman. The role of TNF-α inhibitor in glioma virotherapy: A mathematical model[J]. Mathematical Biosciences and Engineering, 2017, 14(1): 305-319. doi: 10.3934/mbe.2017020

    Related Papers:

  • Virotherapy, using herpes simplex virus, represents a promising therapy of glioma. But the innate immune response, which includes TNF-α produced by macrophages, reduces the effectiveness of the treatment. Hence treatment with TNF-α inhibitor may increase the effectiveness of the virotherapy. In the present paper we develop a mathematical model that includes continuous infusion of the virus in combination with TNF-α inhibitor. We study the efficacy of the treatment under different combinations of the two drugs for different scenarios of the burst size of newly formed virus emerging from dying infected cancer cells. The model may serve as a first step toward developing an optimal strategy for the treatment of glioma by the combination of TNF-α inhibitor and oncolytic virus injection.


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    [1] [ C. Antoni,J. Braun, Side effects of anti-TNF therapy: Current knowledge, Clin Exp Rheumatol, 22 (2002): 152-157.
    [2] [ B. Auffinger,A.U. Ahmed,M.S. Lesniak, Oncolytic virotherapy for malignant glioma: Translating laboratory insights into clinical practice, Front. Oncol., 3 (2013): 1-32.
    [3] [ E.A. Chiocca, Oncolytic viruses, Nat. Rev. Cancer, 2 (2002): 938-950.
    [4] [ L.K. Csatary,G. Gosztonyi,J. Szeberenyi,Z. Fabian,V. Liszka,B. Bodey,C.M. Csatary, MTH-68/H oncolytic viral treatment in human highgrade gliomas, J. Neurooncol, 67 (2004): 83-93.
    [5] [ A. Friedman,J. Tian,G. Fulci,E. Chioca,J. Wang, Glioma virotherapy: Effects of innate immune suppression and increased viral replication capacity, Cancer Res., 66 (2006): 2314-2319.
    [6] [ G. Fulci,L. Breymann,D. Gianni,K. Kurozomi,S.S. Rhee,J. Yu,B. Kaur,D.N. Louis,R. Weissleder,M.A. Caligiuri,E.A. Chiocca, Cyclophosphamide enhances glioma virotherapy by inhibiting innate immune responses, PNAS, 103 (2006): 12873-12878.
    [7] [ I. Ganly,D. Kirn,G. Eckhardt,G.I. Rodriguez,D.S. Soutar,R. Otto,A.G. Robertson,O. Park,M.L. Gulley,C. Heise,D.D. Von Hoff,S.B. Kaye,S.G. Eckhardt, A phase I study of ONYX-015, an EiBattenuated adenovirus, administered intratumorally to patients with recurrent head and neck cancer, Clin. Cancer Res., 6 (2000): 798-806.
    [8] [ M.P. Hallsworth,C.P. Soh,S.J. Lane,J.P. Arm,T.H. Lee, Selective enhancement of GM-CSF, TNF-alpha, IL-1 and IL-8 production by monocytes and macrophages of asthmatic subjects, Eur Respir J., 7 (1994): 1096-1102.
    [9] [ W. Hao,E.D. Crouser,A. Friedman, Mathematical model of sarcoidosis, PNAS, 111 (2014): 16065-16070.
    [10] [ K. Jacobsen,L. Russel,B. Kaur,A. Friedman, Effects of CCN1 and macrophage content on glioma virotherapy: A mathematical model, Bull Math Biol, 77 (2015): 984-1012.
    [11] [ F.R. Khuri,J. Nemunaitis,I. Ganly,J. Arseneau,I.F. Tannock,L. Romel,M. Gore,J. Ironside,R.H. MacDougall,C. Heise,B. Randley,A.M. Gillenwater,P. Bruse,S.B. Kaye,W.K. Hong,D.H. Kirn, A controlled trial of ONYX-015, a selectively-replicating adenovirus, in combination with cisplatin and 5-fluorouracil in patients with recurrent head and neck cancer, Nat. Med., 6 (2000): 879-885.
    [12] [ Y. Kim, H. G. Lee, N. Dmitrieva, J. Kim, B. Kaur and A. Friedman, Choindroitinase ABC I-mediated enhancement of oncolytic virus spread and anti tumor efficacy: A mathematical model PLOS ONE 9 (2014), e102499.
    [13] [ R.M. Lorence,A.L. Pecora,P.P. Major,S.J. Hotte,S.A. Laurie,M.S. Roberts,W.S. Groene,M.K. Bamat, Overview of phase I studies of intravenous administration of PV701, an oncolytic virus, Curr. Opin. Mol. Ther., 5 (2003): 618-624.
    [14] [ J.M. Markert, Conditionally replicating herpes simplex virus mutant, G207 for the treatment of malignant glioma: Results of a phase I trial, Gene. Ther., 7 (2000): 867-874.
    [15] [ W.H. Meisen,E.S. Wohleb,A.C. Jaime-Ramirez,C. Bolyard,J.Y. Yoo,L. Russel,J. Hardcastle,S. Dubin,K. Muili,J. Yu,M. Callgiuri,J. Godbout,B. Kaur, The impact of macrophage-and microglia-secreted TNF-α on oncolitic hsv-1 therapy in the glioblastoma tumor microenvironment, Clin Cancer Res., 21 (2015): 3274-3285.
    [16] [ T. Mineta,S. Rabkin,T. Yazaki,W. Hunter,R. Martuza, Attenuated multi-mutated herpes simplex virus-1 for the treatment of malignant gliomas, Nat. Med., 1 (1995): 938-943.
    [17] [ J.C. Oliver,L.A. Bland,C.W. Oettinger,M.J. Arduino,S.K. McAllister,S.M. Aguero,M.S. Favero, Cytokine kinetics in an in vitro whole blood model following an endotoxin challenge, Lymphokine Cytokine Res., 12 (1993): 115-120.
    [18] [ R. Rodriguez,E.R. Schuur,H.Y. Lim,G.A. Henderson,J.W. Simons,D.R. Henderson, Prostate attenuated replication competent daenovirus (ARCA) CN706: A selective cytotoxic for prostate-specific anti-positive prostate cancer cells, Cancer Res., 57 (2000): 2559-2563.
    [19] [ H. Schättler and U. Ledzewicz, Optimal Control for Mathematical Models of Cancer Therapies Springer Publishing Co., New York, USA, 2015.
    [20] [ G. Wollmann,K. Ozduman,A. N. van den Pol, Oncolytic virus therapy for glioblastoma multiforme: Concepts and candidates, Cancer J., 18 (2012): 69-81.
    [21] [ J.T. Wu,H.M. Byrne,D.H. Kirn,L.M. Wein, Modeling and analysis of a virus that replicates selectively in tumor cells, Bull. Math. Biol., 63 (2001): 731-768.
    [22] [ J.T. Wu,D.H. Kirn,L.M. Wein, Analysis of a three-way race between tumor growth, a replication-competent virus and an immune response, Bull. Math. Biol., 66 (2004): 605-625.
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