“Designer cytokines” targeting the tumor vasculature—think global and act local

Abstract

Tumor necrosis factor (TNF) was discov- ered in 1975 as a lipopolysaccharide- induced serum factor that causes necrosis of tumors (Carswell et al, 1975). It was later found that TNF and cachectin, a factor causing wasting disease, were one and the same molecule (Beutler et al, 1985). Studies on the inflammatory activ- ity of TNF have been translated into clini- cal success, namely blocking antibodies used to suppress autoimmune diseases. Research on TNF anti-tumor activity, in contrast, has not yet resulted in a thera- peutic breakthrough. This may change, based on a study by Huyghe et al (2020) describing novel “designer cytokines” (TNF and interferon-c) that increase local activity by targeting the CD13-positive tumor vasculature, while simultaneously lowering the binding affinity to the respective cytokine receptor, thereby reducing off-target effects on normal cells.