Through the specific and tight interaction between streptavidin and biotin, a novel platform was developed to allow for rapid (less than 2h), efficient and durable display of streptavidin-tagged bioactive GM-CSF on the surface of biotinylated B16.F10 tumor cells. This technology involved biotinylation of the cell membrane with a biotin derivative and surface modification of the biotinylated cells with the bi-functional fusion protein, streptavidin-tagged GM-CSF. Furthermore, the resultant GM-CSF-modified B16.F10 whole tumor cell vaccine could induce strong and long-lasting systemic protection against the wild-type tumor challenge. Therefore, the platform may represent a fast, efficient and safe approach for the whole tumor cell vaccination.