Synergistic anti-tumor effect of glycosylphosphatidylinositol-anchored IL-2 and IL-12

The Journal of Gene Medicine
Jianfei JiYanzhang Wei

Abstract

Preclinical and clinical studies have demonstrated that interleukin 2 (IL-2), interleukin 12 (IL-12), and some other cytokines, play important roles in activating host immune responses against tumor growth. However, severe side effects caused by systemic high-dose administration of these cytokines limit their clinical application. In our previous study, local high doses of IL-2 were achieved by a GPI-anchoring technology; therefore, it will be interesting to know if this technology works for other cytokines. A fusion gene containing murine IL-12 and the glycosylphosphatidylinositol (GPI) anchor signal sequence was generated and transfected into the murine melanoma tumor cell line B16F0 either alone or together with a vector encoding GPI-anchored IL-2. The GPI-anchored cytokine expression of the selected stable clones was assayed in vitro by ELISA and their anti-tumor effects were analyzed in vivo by tumor lymphocyte infiltration and tumor growth studies. GPI-anchored IL-12 was successfully expressed on the cell surface as indicated by FACS analysis and IL-12 ELISA assay. The GPI-anchored IL-12 enhanced lymphocyte infiltration and significantly inhibited tumor growth. More importantly, when GPI-anchored IL-12 and GPI-anchored IL...Continue Reading

Citations

Feb 16, 2012·Molecular Therapy : the Journal of the American Society of Gene Therapy·Wen-Yu PanMi-Hua Tao
Feb 17, 2010·Immune Network·Young Sang Kim
May 16, 2008·Medicinal Research Reviews·Tian-Lu Cheng, Steve Roffler
Apr 16, 2016·International Journal of Oncology·Xi YangYanzhang Wei

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