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Enhancing synergy of CAR T cell therapy and oncolytic virus therapy for pancreatic cancer

Rachel Walker, Pedro E. Navas, Samuel H. Friedman, Simona Galliani, Aleksandra Karolak, Fiona Macfarlane, Robert Noble, Jan Poleszczuk, Shonagh Russell, Katarzyna A. Rejniak, Amir Shahmoradi, Frederik Ziebell, Jason Brayer, Daniel Abate-Daga, Heiko Enderling
doi: https://doi.org/10.1101/055988
Rachel Walker
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Pedro E. Navas
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Samuel H. Friedman
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Simona Galliani
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Aleksandra Karolak
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Fiona Macfarlane
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Robert Noble
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Jan Poleszczuk
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Shonagh Russell
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Katarzyna A. Rejniak
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Amir Shahmoradi
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Frederik Ziebell
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Jason Brayer
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Daniel Abate-Daga
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Heiko Enderling
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Abstract

The poor immunogenicity of pancreatic tumors makes them particularly difficult to treat. Standard chemotherapies and single agent immunotherapies have had notoriously little success in this arena. Oncolytic virus therapy has the potential to enhance the penetration of immunotherapeutically-delivered CAR T cells into the tumor and improve treatment outcomes. We evaluate this potential by combining two different mathematical approaches: an ordinary differential equation model to simulate population level tumor response to cytotoxic activity of T cells, coupled with an agent-based model to simulate the enhancement of CAR T cell penetration by oncolytic virus therapy.

Footnotes

  • Research supported by H. Lee Moffitt Cancer Center & Research Institute.

  • R. W, P. E. N., A. K., J. P., S. R., K. A. R., A. R. A. A., J. B., D. A.-D., H. E. are with the H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612 USA (813-745-3562; fax: 813-745-6497; e-mail: {Jason.Brayer;Daniel.AbateDaga;Heiko.Enderling}@moffitt.org).

  • S. F. Author is with the Center for Applied Molecular Medicine, University of Southern California, Los Angeles, CA 90033 USA

  • S. G. Author is with the Stuttgart Research Center Systems Biology (SRCSB), 70569 Stuttgart, Germany

  • F. M. Author is with the School of Mathematics and Statistics, University of St Andrews, KY16 9SS UK

  • R. N. Author is with the Institut des Sciences de Evolution, University of Montpellier, Montpellier 34095, France

  • A. S. Author is with the Institute for Computational Engineering and Sciences, The University of Texas at Austin, Austin, TX 78712 USA

  • F. Z. Author is with the Institute of Applied Mathematics and the German Cancer Research Center (DKFZ), Heidelberg, Germany

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted May 30, 2016.
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Enhancing synergy of CAR T cell therapy and oncolytic virus therapy for pancreatic cancer
Rachel Walker, Pedro E. Navas, Samuel H. Friedman, Simona Galliani, Aleksandra Karolak, Fiona Macfarlane, Robert Noble, Jan Poleszczuk, Shonagh Russell, Katarzyna A. Rejniak, Amir Shahmoradi, Frederik Ziebell, Jason Brayer, Daniel Abate-Daga, Heiko Enderling
bioRxiv 055988; doi: https://doi.org/10.1101/055988
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Enhancing synergy of CAR T cell therapy and oncolytic virus therapy for pancreatic cancer
Rachel Walker, Pedro E. Navas, Samuel H. Friedman, Simona Galliani, Aleksandra Karolak, Fiona Macfarlane, Robert Noble, Jan Poleszczuk, Shonagh Russell, Katarzyna A. Rejniak, Amir Shahmoradi, Frederik Ziebell, Jason Brayer, Daniel Abate-Daga, Heiko Enderling
bioRxiv 055988; doi: https://doi.org/10.1101/055988

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