Development of Delivery Systems for Local Administration of Cytokines/Cytokine Gene-Directed Therapeutics: Modern Oncologic Implications

Purpose of Review: In this review, we discuss modern cytokine delivery systems in oncologic care, focusing on modalities being developed in the clinical trials or currently in use. These include pegylation, immune-cytokine drug conjugates, cytokine-expressing plasmid nanoparticles, nonviral cytokine nanoparticles, viral systems, and AcTakines. Recent Findings: Cytokine therapy has the potential to contribute to cancer treatment options by modulating the immune system towards an improved antitumor response and has shown promise both independently and in combination with other immunotherapy agents. Despite promising preliminary studies, systemic toxicities and challenges with administration have limited the impact of unmodified cytokine therapy. In the last decade, novel delivery systems have been developed to address these challenges and facilitate cytokine-based oncologic treatments. Summary: Novel delivery systems provide potential solutions to decrease dose-limiting side effects, facilitate administration, and increase the therapeutic activity of cytokine treatments in oncology care. The expanding clinical and translational research in these systems provides an opportunity to augment the armamentarium of immune oncology and may represent the next frontier of cytokine-based immuno-oncology.