Targeted Cytokine Delivery for Cancer Treatment: Engineering and Biological Effects

Anti-tumor properties of several cytokines have already been investigated in multiple experiments and clinical trials. However, those studies evidenced substantial toxicities, even at low cytokine doses, and the lack of tumor specificity. These factors significantly limit clinical applications. Due to their high specificity and affinity, tumor-specific monoclonal antibodies or their antigen-binding fragments are capable of delivering fused cytokines to tumors and, therefore, of decreasing the number and severity of side effects, as well as of enhancing the therapeutic index. The present review surveys the actual antibody-cytokine fusion protein (immunocytokine) formats, their targets, mechanisms of action, and anti-tumor and other biological effects. Special attention is paid to the formats designed to prevent the off-target cytokine-receptor interactions, potentially inducing side effects. Here, we describe preclinical and clinical data and the efficacy of the antibody-mediated cytokine delivery approach, either as a single therapy or in combination with other agents.

Automated summary

The anti-tumor properties of various cytokines have been studied extensively in experiments and clinical trials, but their toxicity and lack of tumor specificity have limited their clinical applications. Utilizing tumor-specific monoclonal antibodies or their fragments to deliver fused cytokines to tumors can minimize side effects and increase therapeutic effectiveness. This review provides an overview of different formats of antibody-cytokine fusion proteins, their targets, mechanisms of action, and biological effects, with a focus on formats that prevent off-target cytokine-receptor interactions to minimize side effects. The efficacy of antibody-mediated cytokine delivery, either as a monotherapy or in combination with other agents, is discussed based on preclinical and clinical data.