Tumor cell surface expression of granulocyte-macrophage colony-stimulatingfactor elicits antitumor immunity and protects from tumor challenge in theP815 mouse mastocytoma tumor model

A novel membrane-bound form of GM-CSF (mbGM-CSF) was expressed on the surfa ce of the mouse mastocytoma cell line P815 to target tumor cell-associated Ags to epidermal Langerhans cells, Transfected clones stimulated the prolif eration of syngeneic bone marrow cells, indicating that mbGM-CSF is biologi cally active. We evaluated the in vivo effects of mbGM-CSF by comparing the growth of mbGM-CSF cells (termed 1D6.1E5) to that of wild-type P815 cells in DBA/2 mice, The growth rates of tumors initiated by P815 and 1D6.1E5 wer e similar until day 12, after which p815 tumors grew to large sizes while 1 D6.1E5 tumors were rejected. In contrast, the growth of both tumors was uni mpeded when injected into nude mice, suggesting that a T cell-dependent ant itumor response was induced by 1D6.1E5 in normal mice, Lymphocytes from 1D6 .1E5-vaccinated mice were able to kill Cr-51-labeled P815 cells in a dose-d ependent fashion that was inhibited by anti-CD8 Abs, suggesting that the an titumor response involved CD8(+) CTL, We then tested whether vaccination wi th these cells would elicit a protective antitumor response by injecting mi ce with either irradiated 1D6.1E5 or P815 cells and challenging them with n onirradiated P815 cells. 1D6.1E5-treated mice grew small tumors that soon d isappeared in all animals, In contrast, the majority of animals receiving t he irradiated wild-type tumor vaccine grew large tumors, and 50% died. Thes e data demonstrate that mbGM-CSF expressed on the surface of tumor cells is biologically active and elicits protective antitumor immunity.