Protein engineering: a driving force toward synthetic immunology

The full application of the diverse toolkit of protein engineering has made it easier to control the immune system. In particular, synthetic cytokine variants and engineered immune receptor platforms have shown promise for the treatment of various indications with dysregulated immune function, particularly cancer. Here, we review recent advances in the control of immune cell signaling and therapeutic potency that have employed protein engineering strategies. We further discuss how safety concerns are driving the design of immunotherapeutics toward 'user-defined' control or requiring multiple distinct inputs before a functional response, highlighting emergent control strategies employed for chimeric antigen receptor (CAR) engineering.