Rethinking Cancer Immunotherapy by Embracing and Engineering Complexity

Highlights

• Complexity theory provides a conceptual framework in which biological and artificial networks may be designed or manipulated to intensify cell bioprocessing in cancer immunotherapies.

• Studies on T cell mechanobiology have revealed how physical parameters may be exploited to perturb intracellular networks as an effective way of controlling T cell fates for immunotherapeutic applications.

• Systems-biology-based computational models open up the potential to predict cues needed to guide T cell differentiation and reprogramming.

• Advances in immunomodulatory biomaterials, microfabrication, and wearable medical technologies raise the possibility of scaling up point-of-care deployment of immunotherapies.

The meteoric rise of cancer immunotherapy in the past decade has led to promising treatments for a number of hard-to-treat malignancies. In particular, adoptive T cell therapy has recently reached a major milestone with two products approved by the US FDA. However, the inherent complexity of cell-based immunotherapies means that their manufacturing time, cost, and controllability limit their effectiveness and geographic reach. One way to address these issues may lie in complementing the dominant, reductionistic mentality in modern medicine with complex systems thinking. In this opinion article, we identify key concepts from complexity theory to address manufacturing challenges in cell-based immunotherapies and raise the possibility of a unifying framework upon which future bioprocessing strategies may be designed.