Adaptive Virotherapy Strategy for Organism With Constrained Input Using Medicine Dosage Regulation Mechanism.

Abstract

In this article, the constrained adaptive control strategy based on virotherapy is investigated for organism using the medicine dosage regulation mechanism (MDRM). First, the tumor-virus-immune interaction dynamics is established to model the relations among the tumor cells (TCs), virus particles, and the immune response. The adaptive dynamic programming (ADP) method is extended to approximately obtain the optimal strategy for the interaction system to reduce the populations of TCs. Due to the consideration of asymmetric control constraints, the nonquadratic functions are proposed to formulate the value function such that the corresponding Hamilton-Jacobi-Bellman equation (HJBE) is derived which can be deemed as the cornerstone of ADP algorithms. Then, the ADP method of a single-critic network architecture which integrates MDRM is proposed to obtain the approximate solutions of HJBE and eventually derive the optimal strategy. The design of MDRM makes it possible for the dosage of the agentia containing oncolytic virus particles to be regulated timely and necessarily. Furthermore, the uniform ultimate boundedness of the system states and critic weight estimation errors is validated by Lyapunov stability analysis. Finally, simulation results are given to show the effectiveness of the derived therapeutic strategy.