Scientific publications

Novel strategies exploiting interleukin-12 in cancer immunotherapy

Nov 1, 2022 | Magazine: Pharmacology & Therapeutics

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


 Abstract

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.

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

Our authors

Assunta Cirella
Claudia Di Trani
Dr. Álvaro Teijeira Sánchez
Irene Olivera Valle
Elixabet Bolaños Mateo
Gestora de Proyectos del Programa de Inmunología e Inmunoterapia del Cima Universidad de Navarra
Belén Palencia Coto
Dr. Fernando Aranda Vega