Systemic IL-12 as an antitumor agent in cancer therapy

SAVID FRONTERA C; BAEZ N ; MARIA CECILIA RODRIGUEZ GALAN

Buenos Aires

Congreso; IV LASID meeting-LXIII Argentinean Society for Immunology Meeting - II French-Argentinean Immunology Meeting; 2015

Sociedad Argentina de Inmunología

Interleukin 12 (IL-12) isa pro-inflamatory cytokine with several anti-tumoral properties. Recombinant IL-12 iscurrently assayed as treatment of different type of cancer in clinical trials. Here,we evaluated both the antitumor effect and the cellular composition of thelymph nodes that drain the tumors after systemic expression of IL-12. We observed that the elevated seralevels of IL-12 found 24h-48h after hydrodynamic injection of its naked cDNA significantlyattenuate tumor growth in a B16 melanoma model measured by the size and theweight of the tumors. Interestingly, the size of the tumors correlates with theIL-12 sera levels (higher IL-12 levels, lower tumor size). Macroscopicallyanalysis revealed that IL-12 treatment induced a diminution in the vascularirrigation of the tumors compared to control mice. Examination of the tumordraining and non-draining lymph nodes demonstrated a significant reduction inthe total cell number that correlate with a diminution of CD4+ Tcells and CD11b+Gr1lo cells in IL-12-treated mice. We alsoobserved that IL-12 systemic expression generate a significant expansion ofsplenic cells determined by the size of the organ and the total cell count.When splenocytes of IL-12-treated mice were co-culture with YAC-1 tumor cell,we observed a significant increased in their killing capacity compared tosplenocytes from control mice. All together, our dataindicates that systemic IL-12 expression is able to generate a high antitumoralcapacity by inducing an angiostatic effect in the tumor and changes in thecomposition and cytotoxic ability of immune cells of secondary immune organs.