Cytokines exert a vast array of immunoregulatory actions critical to human biology and
disease. However, the desired immunotherapeutic effects of native cytokines are often
mitigated by toxicity or lack of efficacy, either of which results from cytokine receptor
pleiotropy and/or undesired activation of off-target cells. As our understanding of the
structural principles of cytokine–receptor interactions has advanced, mechanism-based
manipulation of cytokine signaling through protein engineering has become an increasingly …