A modeling platform for the lymphatic system

J Theor Biol. 2020 May 21:493:110193. doi: 10.1016/j.jtbi.2020.110193. Epub 2020 Feb 28.

Abstract

We present a physiologically-based pharmacokinetic modeling platform capable of simulating the biodistribution of different therapeutic agents, including cells, their interactions within the immune system, redistribution across lymphoid compartments, and infiltration into tumor tissues. This transport-based platform comprises a distinctive implementation of a tumor compartment with spatial heterogeneity which enables the modeling of tumors of different size, necrotic state, and agent infiltration capacity. We provide three validating and three exploratory examples that illustrate the capabilities of the proposed approach. The results show that the model can recapitulate immune cell balance across different compartments, respond to antigen stimulation, simulate immune vaccine effects, and immune cell infiltration to tumors. Based on the results, the model can be used to study problems pertinent to current immunotherapies and has the potential to assist medical techniques that rely on the transport of biological species.

Keywords: Cancer; Immunotherapy; Lymphatic system; Mathematical modeling; Physiologically-based pharmacokinetic modeling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Immunotherapy*
  • Lymphatic System
  • Neoplasms* / therapy
  • Tissue Distribution