Novel strategies exploiting interleukin-12 in cancer immunotherapy
Assunta Cirella 1 , Carlos Luri-Rey 1 , Claudia Augusta Di Trani 1 , Alvaro Teijeira 2 , Irene Olivera 1 , Elixabet Bolaños 1 , Eduardo Castañón 3 , Belen Palencia 4 , Davide Brocco 5 , Myriam Fernández-Sendin 1 , Fernando Aranda 1 , Pedro Berraondo 6 , Ignacio Melero 7
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.