Melanoma differentiation-associated gene-7 (mda-7)/interleukin (IL)-24 induces anticancer immunity in a syngeneic murine model
- 10 March 2006
- journal article
- Published by Springer Science and Business Media LLC in Cancer Gene Therapy
- Vol. 13 (8), 753-761
- https://doi.org/10.1038/sj.cgt.7700954
Abstract
Previous studies have shown that the human melanoma differentiation-associated gene-7 (mda-7)/interleukin-24 (IL-24) has tumor-suppressor activity in vitro and in vivo. Additionally, in vitro studies using human peripheral blood mononuclear cells indicate that mda-7/IL-24 has TH1 cytokine-like activity. However, the individual properties of mda-7/IL-24 have been previously examined separately. Thus, there is not a single study that has examined both, antitumor and proimmune properties of mda-7/IL-24. Furthermore, the tumor suppressive activity and the cytokine activity of mda-7/IL-24 have not been previously tested in an immunocompetent setting. We therefore in the present study evaluated the antitumor and immune properties of mda-7/IL-24 in a murine syngeneic tumor model. In vitro, adenovirus-mediated mda-7 gene (Ad-mda7) transfer to murine fibrosarcoma (UV2237m; MCA16) and normal (10T1/2) cells significantly inhibited growth (P=0.001) and induced apoptosis in tumor cells but not in normal cells. In vivo, intratumoral administration of Ad-mda7 resulted in significant inhibition of tumor growth (Pin vitro subset analysis of splenocytes from vaccinated mice demonstrated a significant increase in the CD3+CD8+ but not the CD3+CD4+ cell population (P=0.019). Thus Ad-mda7 treatment of syngeneic tumors induces tumor cell death and promotes immune activation, leading to anticancer immunity.Keywords
This publication has 26 references indexed in Scilit:
- Bystander activity of Ad-mda7: Human MDA-7 protein kills melanoma cells via an IL-20 receptor-dependent but STAT3-independent mechanismMolecular Therapy, 2004
- Gene transfer approaches in cancer immunotherapyGene Therapy, 2004
- Adenovirus-mediated mda-7 (IL24) gene therapy suppresses angiogenesis and sensitizes NSCLC xenograft tumors to radiationMolecular Therapy, 2004
- Inhibition of human lung cancer growth following adenovirus-mediated mda-7 gene expression in vivoOncogene, 2002
- Successful Treatment of Primary and Disseminated Human Lung Cancers by Systemic Delivery of Tumor Suppressor Genes Using an Improved Liposome VectorMolecular Therapy, 2001
- Tumor-suppressive effects by adenovirus-mediated mda-7 gene transfer in non-small cell lung cancer cell in vitroGene Therapy, 2000
- Reexpression Following Readministration of an Adenoviral Vector in Adult Mice after Initial in Utero Adenoviral AdministrationMolecular Therapy, 2000
- Therapeutic Vaccination for CancerClinical Immunology, 2000
- Stable Expression of the Wild-Typep53Gene in Human Lung Cancer Cells after Retrovirus-Mediated Gene TransferHuman Gene Therapy, 1993
- Interleukin 2 gene transfer into tumor cells abrogates tumorigenicity and induces protective immunity.The Journal of Experimental Medicine, 1990