Zeitschrift für Glykobiologie
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Novel Cancer Vaccination System Based on Human Endo-Β-N-Acetyl Glucosaminidase Gene Delivery

Satoshi Watanabe, Seiki Haraguchi, Shingo Nakamura, Takayuki Sakurai, Shin-ichiro Mugikura, Kagemasa Kajiwara, Minoiru Kimura and Masahiro Sato

Cancer vaccination elicits an immune response against specific glycans or proteins expressed on the cell surface after gene transfer has occurred. We previously demonstrated that N-acetylglucosamine (GlcNAc) residues exposed after digestion with endo-β-galactosidase, a carbohydrate-digesting enzyme, elicited this type of immune response, probably as a result of the presence of natural antibodies recognizing GlcNAc residues in host animals. Treatment of a cell with endo-β-N-acetylglucosaminidase (ENGase), an enzyme that cleaves the amide bond between the proximal GlcNAc residues at the side chain of an asparagine residue on N-glycans, also causes exposure of GlcNAc residues on the cell surface. In this study, we examined whether mouse melanoma B16 cells transfected with a human ENGase (hENGase) cDNA expression construct, are susceptible to an immune attack after subcutaneous grafting to the syngenic host. The recombinant B16 cells overexpressing hENGase had approximately 3-fold more cell-surface GlcNAc residues than their parental cells. The grafting experiment revealed that the tumor size was approximately one-tenth of that derived from wild-type grafted cells. Direct injection and subsequent in vivo electroporation of a hENGase expression vector into B16 solid tumors resulted in regression of the tumors. Our present results strongly suggest that the ENGase is a useful tool for novel cancer vaccination.