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| Recent experiments with engineered oncolytic adenovirus have caused substantial reduction in growth rates of tumors in mice. We develop mathematical models based on data from four different treatments: (Ad) oncolytic adenovirus, (Ad/4-1BBL) Ad virus co-expressing the molecule 4-1BBL, (Ad/IL-12) Ad virus co-expressing the cytokine IL-12, and (Ad/4-1BBL/IL-12) Ad virus co-expressing both 4-1BBL and IL-12.
By fitting time series data of tumor growth to mathematical models, we attempt to elucidate the underlying cancer-virus and cancer-immune dynamics to clarify the strengths and limitations of oncolytic virotherapy and suggest improved methods of treatment. Using modeling, we consider how existing oncolytic adenoviruses can be used to (1) rapidly kill the tumor with a goal of complete elimination or (2) maintain the tumor long-term at low levels. We also consider the possibility of using two specialist viruses, Ad/4-1BBL and Ad/IL-12, instead of the more general virus, Ad/4-1BBL/IL-12. We also show how increases in viral burst size or immunostimulatory capability could affect treatment outcomes. |
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