A quantitative systems pharmacology perspective on cancer immunology

Abstract

The return on investment within the pharmaceutical industry has exhibited an exponential decline over the last several decades. Contemporary analysis suggests that the rate-limiting step associated with the drug discovery and development process is our limited understanding of the disease pathophysiology in humans that is targeted by a drug. Similar to other industries, mechanistic modeling and simulation has been proposed as an enabling quantitative tool to help address this problem. Moreover, immunotherapies are transforming the clinical treatment of cure cancer and are becoming a major segment of the pharmaceutical research and development pipeline. As the clinical benefit of these immunotherapies seems to be limited to subset of the patient population, identifying the specific defect in the complex network of interactions associated with host immunity to a malignancy is a major challenge for expanding the clinical benefit. Understanding the interaction between malignant and immune cells is inherently a systems problem, where an engineering perspective may be helpful. The objective of this manuscript is to summarize this quantitative systems perspective, particularly with respect to developing immunotherapies for the treatment of cancer.