Enhancing dendritic cell immunotherapy for melanoma using a simple mathematical model

Tello del Castillo, José Ignacio and Castillo-Montiel, E. and Chimal-Eguía, J. C. and Piñon-Zárate, G. and Herrera-Enríquez, M. and Castell-Rodríguez, A. E. (2015). Enhancing dendritic cell immunotherapy for melanoma using a simple mathematical model. "Theoretical biology and medical modelling" ; pp. 1-14. ISSN 1742-4682. https://doi.org/10.1186/s12976-015-0007-0.

Description

Title: Enhancing dendritic cell immunotherapy for melanoma using a simple mathematical model
Author/s:
  • Tello del Castillo, José Ignacio
  • Castillo-Montiel, E.
  • Chimal-Eguía, J. C.
  • Piñon-Zárate, G.
  • Herrera-Enríquez, M.
  • Castell-Rodríguez, A. E.
Item Type: Article
Título de Revista/Publicación: Theoretical biology and medical modelling
Date: 2015
ISSN: 1742-4682
Subjects:
Freetext Keywords: Keywords: Mathematical model, Cancer, Melanoma, Immunotherapy, Dendritic cell, TGF − β cytokine
Faculty: E.T.S.I. de Sistemas Informáticos (UPM)
Department: Matemática Aplicada a las Tecnologías de la Información y las Comunicaciones
Creative Commons Licenses: Recognition - No derivative works - Non commercial

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Abstract

ABSTRACT Background: The immunotherapy using dendritic cells (DCs) against different varieties of cancer is an approach that has been previously explored which induces a specific immune response. This work presents a mathematical model of DCs immunotherapy for melanoma in mice based on work by Experimental Immunotherapy Laboratory of the Medicine Faculty in the Universidad Autonoma de Mexico (UNAM). Method: The model is a five delay differential equation (DDEs) which represents a simplified view of the immunotherapy mechanisms. The mathematical model takes into account the interactions between tumor cells, dendritic cells, naive cytotoxic T lymphocytes cells (inactivated cytotoxic cells), effector cells (cytotoxic T activated cytotoxic cells) and transforming growth factor β cytokine (TGF − β). The model is validated comparing the computer simulation results with biological trial results of the immunotherapy developed by the research group of UNAM. Results: The results of the growth of tumor cells obtained by the control immunotherapy simulation show a similar amount of tumor cell population than the biological data of the control immunotherapy. Moreover, comparing the increase of tumor cells obtained from the immunotherapy simulation and the biological data of the immunotherapy applied by the UNAM researchers obtained errors of approximately 10 %. This allowed us to use the model as a framework to test hypothetical treatments. The numerical simulations suggest that by using more doses of DCs and changing the infusion time, the tumor growth decays compared with the current immunotherapy. In addition, a local sensitivity analysis is performed; the results show that the delay in time “τ ”, the maximal growth rate of tumor “r” and the maximal efficiency of tumor cytotoxic cells rate “aT” are the most sensitive model parameters. Conclusion: By using this mathematical model it is possible to simulate the growth of the tumor cells with or without immunotherapy using the infusion protocol of the UNAM researchers, to obtain a good approximation of the biological trials data. It is worth mentioning that by manipulating the different parameters of the model the effectiveness of the immunotherapy may increase. This last suggests that different protocols could be implemented by the Immunotherapy Laboratory of UNAM in order to improve their results.

More information

Item ID: 44757
DC Identifier: http://oa.upm.es/44757/
OAI Identifier: oai:oa.upm.es:44757
DOI: 10.1186/s12976-015-0007-0
Official URL: https://tbiomed.biomedcentral.com/articles/10.1186/s12976-015-0007-0
Deposited by: Memoria Investigacion
Deposited on: 27 Apr 2017 16:46
Last Modified: 27 Apr 2017 21:54
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