Modeling of cancer virotherapy with recombinant measles viruses.
The Edmonston vaccine strain of measles virus has potent and selective activity against a wide range of tumors. Tumor cells infected by this virus or genetically modified strains express viral proteins that allow them to fuse with neighboring cells to form syncytia that ultimately die. Moreover, infected cells may produce new virus particles that proceed to infect additional tumor cells. We present a model of tumor and virus interactions based on established biology and with proper accounting of the free virus population. The range of model parameters is estimated by fitting to available experimental data. The stability of equilibrium states corresponding to complete tumor eradication, therapy failure and partial tumor reduction is discussed. We use numerical simulations to explore conditions for which the model predicts successful therapy and tumor eradication. The model exhibits damped, as well as stable oscillations in a range of parameter values. These oscillatory states are organized by a Hopf bifurcation.
Bajzer
Zeljko
Z
Biomathematics Resource and Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Guggenheim 1611b, Rochester, MN 55905, USA. bajzer@mayo.edu
Carr
Thomas
T
Josić
Kresimir
K
Russell
Stephen J
SJ
Dingli
David
D
D000818:Animals; D002455:Cell Division; D006801:Humans; D008459:Measles virus; D051379:Mice; D016513:Mice, SCID; D008954:Models, Biological; D009101:Multiple Myeloma / Q000473:pathology / Q000628:therapy; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000473:pathology / Q000628:therapy* / Q000821:virology; D050130:Oncolytic Virotherapy / Q000379:methods*; D050504:Oncolytic Viruses; D011379:Prognosis; D014183:Transplantation, Heterologous; D016896:Treatment Outcome