Cancer immunotherapy, mathematical modeling and optimal control

Clinical immunologists, among other problems, routinely face a question: what is the best time and dose for a certain therapeutic agent to be administered to the patient in order to decrease/eradicate the pathological condition? In cancer immunotherapies the therapeutic agent is something able to elicit an immune response against cancer. The immune response has its own dynamics that depends on the inummogenicity of the therapeutic agent and on the duration of the immune response. The question then is how can we decide when and hon, much of the drug to inject so to have a prolonged and effective immune response to the cancer?. This question can be addressed in mathematical terms in two stages: first one construct a mathematical model describing the cancerimmune interaction and secondly one applies the theory of optimal control to determine when and to which extent to stimulate the immune system by means of an immunotherapeutic agent administered in discrete variable doses within the therapeutic period. The solution of this mathematical problem is described and discussed in this article. We show that the method employed can be applied to find the optimal protocol in a variety of clinical problems where the kinetics of the drug or treatment and its influence on the physiologic/pathologic functions have been described by a system of ordinary differential equations. (c) 2007 Elsevier Ltd. All rights reserved.