Stochastic optimal therapy for enhanced immune response

Mathematical Biosciences
Robert F Stengel, Raffaele M Ghigliazza

Abstract

Therapeutic enhancement of humoral immune response to microbial attack is addressed as the stochastic optimal control of a dynamic system. Without therapy, the modeled immune response depends upon the initial concentration of pathogens in a simulated attack. Immune response can be augmented by agents that kill the pathogen directly, that stimulate the production of plasma cells or antibodies, or that enhance organ health. Using a generic mathematical model of immune response to the infection (i.e., of the dynamic state of the system), previous papers demonstrated optimal (open-loop) and neighboring-optimal (closed-loop) control solutions that defeat the pathogen and preserve organ health, given initial conditions that otherwise would be lethal [Optimal Contr. Appl. Methods 23 (2002) 91, Bioinformatics 18 (2002) 1227]. Therapies based on separate and combined application of the agents were derived by minimizing a quadratic cost function that weighted both system response and drug usage, providing implicit control over harmful side effects. Here, we focus on the effects that corrupted or incomplete measurements of the dynamic state may have on neighboring-optimal feedback control. Imperfect measurements degrade the precision of f...Continue Reading

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Citations

Jan 6, 2007·Journal of Mathematical Biology·O Krakovska, L M Wahl
Feb 14, 2009·Computer Methods and Programs in Biomedicine·Radhakant Padhi, Jayender R Bhardhwaj
Jun 7, 2008·Journal of Theoretical Biology·Bor-Sen ChenYung-Jen Chuang
Apr 22, 2006·Value in Health : the Journal of the International Society for Pharmacoeconomics and Outcomes Research·John A Vernon, W Keener Hughen
Apr 29, 2008·Mathematical Biosciences·Robert F Stengel
Nov 30, 2019·Cellular and Molecular Life Sciences : CMLS·Jan EwaldBashar Ibrahim

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