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?:abstract
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Interleukin-12 (IL-12) is a potent, pro-inflammatory type 1 cytokine that has long been studied as a potential immunotherapy for cancer. Unfortunately, IL-12\'s remarkable antitumor efficacy in preclinical models has yet to be replicated in humans. Early clinical trials in the mid-1990\'s showed that systemic delivery of IL-12 incurred dose-limiting toxicities. Nevertheless, IL-12\'s pleiotropic activity, i.e., its ability to engage multiple effector mechanisms and reverse tumor-induced immunosuppression, continues to entice cancer researchers. The development of strategies which maximize IL-12 delivery to the tumor microenvironment while minimizing systemic exposure are of increasing interest. Diverse IL-12 delivery systems, from immunocytokine fusions to polymeric nanoparticles, have demonstrated robust antitumor immunity with reduced adverse events in preclinical studies. Several localized IL-12 delivery approaches have recently reached the clinical stage with several more at the precipice of translation. Taken together, localized delivery systems are supporting an IL-12 renaissance which may finally allow this potent cytokine to fulfill its considerable clinical potential. This review begins with a brief historical account of cytokine monotherapies and describes how IL-12 went from promising new cure to ostracized black sheep following multiple on-study deaths. The bulk of this comprehensive review focuses on developments in diverse localized delivery strategies for IL-12-based cancer immunotherapies. Advantages and limitations of different delivery technologies are highlighted. Finally, perspectives on how IL-12-based immunotherapies may be utilized for widespread clinical application in the very near future are offered.
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?:doi
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?:doi
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10.3389/fimmu.2020.575597
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document_parses/pdf_json/a4210c9f23b25877535ba5f465849d6134c7cce8.json
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document_parses/pmc_json/PMC7593768.xml.json
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?:title
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Localized Interleukin-12 for Cancer Immunotherapy
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