Tumor control, elimination, and escape through a compartmental model of dendritic cell therapy for melanoma

Lauren R. Dickman, Evan Milliken, Yang Kuang

Research output: Contribution to journalArticle

Abstract

Melanoma, the deadliest form of skin cancer, is regularly treated by surgery in conjunction with a targeted therapy or immunotherapy. Dendritic cell therapy is an immunotherapy that capitalizes on the critical role dendritic cells play in shaping the immune response. We formulate a mathematical model employing ordinary differential and delay differential equations to understand the effectiveness of dendritic cell vaccines, accounting for cell trafficking with a blood and tumor compartment. We reduce our model to a system of ordinary differential equations. Both models are validated using experimental data from melanoma-induced mice. The simplicity of our reduced model allows for mathematical analysis and admits rich dynamics observed in a clinical setting, such as periodic solutions and bistability. We give thresholds for tumor elimination and existence. Bistability, in which the model outcomes are sensitive to the initial conditions, emphasizes a need for more aggressive treatment strategies, since the reproduction number below unity is no longer sufficient for elimination. A sensitivity analysis exhibits the parameters most significantly impacting the reproduction number, thereby suggesting the most efficacious treatments to use together with a dendritic cell vaccine.

Original languageEnglish (US)
Pages (from-to)906-928
Number of pages23
JournalSIAM Journal on Applied Mathematics
Volume80
Issue number2
DOIs
StatePublished - Jan 1 2020

Keywords

  • Backward bifurcation
  • Dendritic cell therapy
  • Hopf bifurcation
  • Partial rank correlation coefficient
  • Stability analysis

ASJC Scopus subject areas

  • Applied Mathematics

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