Safety levels of systemic IL-12 induced by cDNA expression as a cancer therapeutic

Author:

Savid-Frontera Constanza1ORCID,Viano Maria E1ORCID,Baez Natalia S1ORCID,Reynolds Della2,Matellon Mariana1,A Young Howard2ORCID,Rodriguez-Galan Maria C1ORCID

Affiliation:

1. Inmunología, CIBICI-CONICET, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, 5000, Argentina

2. Cancer & Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702-1201 USA

Abstract

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.

Funder

Intramural Research Program of the Center for Cancer Research, National Cancer Institute

Secretaria de Ciencia y Tecnología-UNC

Fundación para el Progreso de la Medicina

Publisher

Future Medicine Ltd

Subject

Oncology,Immunology,Immunology and Allergy

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