Interleukin-12 as an in situ cancer vaccine component: a review

Abstract

Interleukin-12 (IL-12) is a type I cytokine involved in both innate and adaptive immunity that stimulates T and natural killer cell activity and induces interferon gamma production. IL-12 has been identified as a potential immunotherapeutic component for combinatorial cancer treatments. While IL-12 has successfully been used to treat a variety of cancers in mice, it was associated with toxicity when administered systemically in cancer patients. In this review, we discuss the research findings and progress of IL-12 used in combination with other cancer treatment modalities. We describe different methods of IL-12 delivery, both systemic and local, and ultimately highlight the potential of an in situ vaccination approach for minimizing toxicities and providing antitumor efficacy. This review offers a basis for pursuing an in situ vaccine approach that may eventually allow IL-12 to be more readily integrated as an immunotherapy into the clinical treatment of cancers.

Keywords: Cancer immunotherapy; In situ cancer vaccine; Interleukin-12; Local delivery; Targeted delivery.

Fig. 1

Role of IL-12 in innate and adaptive immunity. IL-12 is produced by activated APCs. IL-12 acts predominantly on lymphocytes such as T and NK cells. Stimulation by IL-12 causes these cells to increase their secretion of IFN-γ, further activating tumor-suppressing immune responses. IL-12 and IFN-γ amplifying signals enhance the cytotoxic activities of NK and CD8 + T cells and the cytokine response of CD4 + T cells. IL-10 and TGFβ produced in the TME inhibit secretion of IL-12. Created with BioRender.com

Fig. 2

Methods of IL-12 delivery. Schematic representation of targeted delivery and/or in situ tumor vaccination strategies that have been used to deliver IL-12 to the TME with the potential to reduce IL-12-related toxicity. Created with BioRender.com