ABSTRACT

The ability of cytokines to boost the immune system's activity against tumors has been of pharmaceutical interest for many years, and a number of different cytokines have been investigated in clinical trials. However, complete cures were rarely observed upon systemic administration of recombinant cytokine products, because severe dose-limiting toxicities and unfavorable pharmacokinetic properties prevented the escalation to therapeutically relevant dose regimens. Antibody-cytokine fusion proteins (termed immunocytokines) represent an elegant strategy to improve the therapeutic index of cytokine payloads. The immunoglobulin moiety, used either as a full-size monoclonal antibody or an antibody fragment, serves as a selective delivery vehicle to the site of disease, thereby allowing a preferential accumulation in the malignant environment while sparing healthy tissue. In the past few years, a large number of immunocytokines have been developed and tested in preclinical cancer models, and 10 immunocytokines have further been evaluated in clinical trials for oncological indications. In this review, we discuss the main structural and functional features of immunocytokines, which are relevant for in vivo performance, and outline emerging trends for product development.