Antibody-cytokine Fusion Proteins: Biopharmaceuticals with Immunomodulatory Properties for Cancer Therapy

Cytokines have long been used for therapeutic applications in cancer patients. Substantial side effects and unfavorable pharmacokinetics limit their application and may prevent dose escalation to therapeutically active regimens. Antibody-cytokine fusion proteins (often referred to as immunocytokines) may help localize immunomodulatory cytokine payloads to the tumor, thereby activating anticancer immune responses. A variety of formats (e.g., intact IgGs or antibody fragments), molecular targets (e.g., extracellular matrix components and cell membrane antigens) and cytokine payloads have been considered for the development of this novel class of biopharmaceuticals. This review presents the basic concepts on the design and engineering of immunocytokines, reviews their potential limitations, points out emerging opportunities and summarizes key features of preclinical and clinical-stage products.