The anti-tumor effect of the IFNγ/Fas chimera expressed on CT26 tumor cells.

Abstract

Interferon gamma (IFNγ) is well-known for its ability to stimulate immune cells in response to pathogen infections and cancer. To develop an effective cancer therapeutic vaccine, CT26 colon carcinoma cells were genetically modified to express IFNγ either as a secreted form (sIFNγ) or as a membrane-bound form. For the membrane-bound expression, IFNγ was fused with Fas (mbIFNγ/Fas), incorporating the extracellular cysteine-rich domains, transmembrane, and cytoplasmic domains of Fas. The tumor cells expressing sIFNγ and mbIFNγ/Fas showed slower growth rates compared to the mock-transfected cells. Furthermore, the tumorigenicity of the CT26 cells expressing mbIFNγ/Fas was significantly lower than that of cells expressing sIFNγ or the mock control. Remarkably, about 85% of the mice injected with the mbIFNγ/Fas-expressing tumors remained tumor-free for over two months. Mice that rejected mbIFNγ/Fas-expressing tumors developed systemic anti-tumor immunity against CT26 cells, which was characterized by enhanced levels of CD4⁺ and CD8⁺ T cells, as well as natural killer (NK) cells. Interestingly, splenocytes activated with the mbIFNγ/Fas-expressing tumors exhibited higher cytotoxicity than those activated with tumor cells expressing sIFNγ. These findings suggest that expressing the mbIFNγ/Fas chimera in tumor cells could be a promising strategy for developing whole tumor cell vaccines or gene therapies for cancer immunotherapy.