Safety levels of systemic IL-12 induced by cDNA expression as a cancer therapeutic.
Aim: The aim of this work is to utilize a gene expression procedure to safely express systemic IL-12 and evaluate its effects in mouse tumor models. Materials & methods: Secondary lymphoid organs and tumors from EL4 and B16 tumor-bearing mice were analyzed by supervised and unsupervised methods. Results: IL-12 cDNA induced systemic IL-12 protein levels lower than the tolerated dose in patients. Control of tumor growth was observed in subcutaneous B16 and EL4 tumors. Systemic IL-12 expression induced a higher frequency of both total tumor-infiltrated CD45+ cells and proliferative IFN-γ+CD8+ T cells along with a lower frequency of CD4+FOXP3+ and CD11b+Gr-1+ cells. Conclusion: This approach characterizes the systemic effects of IL-12, helping to improve treatment of metastases or solid tumors.
['Savid-Frontera|Constanza|C|0000-0001-8614-3528', 'Viano|Maria E|ME|0000-0001-5107-928X', 'Baez|Natalia S|NS|0000-0002-5178-228X', 'Reynolds|Della|D|', 'Matellon|Mariana|M|', 'A Young|Howard|H|0000-0002-3118-5111', 'Rodriguez-Galan|Maria C|MC|0000-0002-5703-3116']
systemic IL-12 cancer secondary lymphoid organs EL4 B16 CD8+ T cells IFN-γ hydrodynamic injection immunotherapy tumor microenvironment