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In this paper a mathematical model is presented that describes growth, immune escape, and siRNA treatment of tumors. The model consists of asystem of nonlinear, ordinary differential equations describing tumorcells and immune effectors, as well as the immuno-stimulatory andsuppressive cytokines IL-2 and TGF-. TGF- suppresses theimmune system by inhibiting the activation of effector cells andreducing tumor antigen expression. It also stimulates tumor growth bypromoting angiogenesis, explaining the inclusion of an angiogenicswitch mechanism for TGF- activity. The model predicts thatincreasing the rate of TGF- production for reasonable values oftumor antigenicity enhances tumor growth and its ability to escapehost detection. The model is then extended to include siRNA treatmentwhich suppresses TGF- production by targeting the mRNA that codesfor TGF-, thereby reducing the presence and effect of TGF-in tumor cells. Comparison of tumor response to multiple injectionsof siRNA with behavior of untreated tumors demonstrates theeffectiveness of this proposed treatment strategy. A secondadministration method, continuous infusion, is included to contrastthe ideal outcome of siRNA treatment. The model's results predict conditionsunder which siRNA treatment can be successful in returning anaggressive, TGF- producing tumor to its passive, non-immuneevading state.
Arciero et al. (Thu,) studied this question.