Novel strategies exploiting interleukin-12 in cancer immunotherapy

Pharmacol Ther. 2022 Nov:239:108189. doi: 10.1016/j.pharmthera.2022.108189. Epub 2022 Apr 14.


Interleukin-12 is considered a potent agent to enhance antitumor immune responses. It belongs to a family of heterodimeric cytokines with key roles in the up-regulation and down-regulation of cellular immunity. Since its discovery, recombinant IL-12 was found to exert potent antitumor effects in rodent tumor models and was rapidly tested in the clinic with an unfavorable benefit/toxicity profile. Localized delivery of IL-12 dramatically improves the therapeutic index and this approach is being applied in the clinic based on in-vivo electroporation of naked plasmid DNA encoding IL-12, mRNA formulations, viral vectors and tumor-targeted fusion proteins. Other biotechnology strategies such as IL-12-engineered local adoptive cell therapy and pro-cytokines can also be used to improve results and broaden the therapeutic window. Combination strategies of such localized IL-12-based approaches with checkpoint inhibitors are yielding promising results both preclinically and in the early-phase clinical trials.

Keywords: Adoptive T cell therapy; And RNA-mediated delivery; Expression plasmids; Fusion proteins; Interleukin-12; Localized delivery; Viral vectors.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Genetic Vectors
  • Humans
  • Immunologic Factors
  • Immunotherapy / methods
  • Immunotherapy, Adoptive
  • Interleukin-12* / genetics
  • Neoplasms* / therapy


  • Interleukin-12
  • Immunologic Factors