Systemic IL-12 as an antitumor agent in cancer therapy

SAVID FRONTERA CONSTANZA; BAEZ NATALIA SOLEDAD; RODRIGUEZ-GALÁN MARIA CECILIA

Buenos Aires

Congreso; LXIII Argentinean Immunology Society Meeting; 2015

Interleukin 12 (IL-12) is a pro-inflamatory cytokine with several anti-tumoral properties.Recombinant IL-12 is currently assayed as treatment of different type of cancer in clinical trials. Here,we evaluated both the antitumor effect and the cellular composition of the lymph nodes that drain the tumors after systemic expression of IL-12. We observed that the elevated sera levels of IL-12 found 24h-48h after hydrodynamic injection of its naked cDNA significantly attenuate tumor growth in a B16 melanoma model measured by the size and the weight of the tumors(p<0,05). Interestingly, the size of the tumors correlates with the IL-12 sera levels (higher IL-12 levels, lower tumor size). Macroscopically analysis revealed that IL-12 treatment induced a diminution in the vascular irrigation of the tumors compared to control mice. Examination of the tumor draining and non-draining lymph nodes demonstrated a significant reduction in the total cell number that correlate with a diminution of CD4+ T cells and CD11b+Gr1lo cells in IL-12-treated mice(p<0,05). We also observed that IL-12 systemic expression generate a significant expansion of splenic 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 killingcapacity compared to splenocytes from control mice(p<0,05).All together, our data indicates that systemic IL-12 expression is able to generate a high antitumoral capacity by inducing an angiostatic effect in the tumor and changes in the composition and cytotoxic ability of immune cells of secondary immune organs