Safety levels of systemic IL-12 induced by cDNA expression as a cancer therapeutic.
Constanza Savid-FronteraMaria Estefania VianoNatalia S BaezDella ReynoldsMariana MatellonHoward A YoungMaria Cecilia Rodriguez-GalanPublished in: Immunotherapy (2021)
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.
Keyphrases
- gene expression
- induced apoptosis
- poor prognosis
- machine learning
- end stage renal disease
- drug induced
- chronic kidney disease
- dna methylation
- type diabetes
- metabolic syndrome
- newly diagnosed
- binding protein
- cell proliferation
- cell death
- papillary thyroid
- ejection fraction
- signaling pathway
- prognostic factors
- peritoneal dialysis
- endoplasmic reticulum stress
- dendritic cells
- adipose tissue
- young adults
- nk cells
- patient reported