Dynamics of melanoma tumor therapy with vesicular stomatitis virus: Explaining the variability in outcomes using mathematical modeling

D. M. Rommelfanger, C. P. Offord, J. Dev, Z. Bajzer, R. G. Vile, D. Dingli

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Tumor selective, replication competent viruses are being tested for cancer gene therapy. This approach introduces a new therapeutic paradigm due to potential replication of the therapeutic agent and induction of a tumor-specific immune response. However, the experimental outcomes are quite variable, even when studies utilize highly inbred strains of mice and the same cell line and virus. Recognizing that virotherapy is an exercise in population dynamics, we utilize mathematical modeling to understand the variable outcomes observed when B16ova malignant melanoma tumors are treated with vesicular stomatitis virus in syngeneic, fully immunocompetent mice. We show how variability in the initial tumor size and the actual amount of virus delivered to the tumor have critical roles on the outcome of therapy. Virotherapy works best when tumors are small, and a robust innate immune response can lead to superior tumor control. Strategies that reduce tumor burden without suppressing the immune response and methods that maximize the amount of virus delivered to the tumor should optimize tumor control in this model system.

Original languageEnglish (US)
Pages (from-to)543-549
Number of pages7
JournalGene Therapy
Volume19
Issue number5
DOIs
StatePublished - May 2012

Keywords

  • cancer gene therapy
  • heterogeneity
  • initial conditions
  • mathematical modeling
  • nonlinear least square fitting
  • virotherapy

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Fingerprint Dive into the research topics of 'Dynamics of melanoma tumor therapy with vesicular stomatitis virus: Explaining the variability in outcomes using mathematical modeling'. Together they form a unique fingerprint.

  • Cite this