Augmentation of antitumor immunity using genetically M-CSF-expressing L1210 cells.

ABSTRACT

Macrophage colony-stimulating factor (M-CSF) enhances tumoricidal activities of macrophages. We transduced human M-CSF cDNA into the mouse lymphoid cell line, L1210, and examined the antitumor effect of the locally expressed M-CSF. Mice injected with the M-CSF-producing subline showed improved survival in comparison with the mock-transfected cell line or parental cell line plus M-CSF administration (20 microg/kg for 3 days) at inoculated cell numbers of 10(2) or 5 x 10(3). The survival rate at 50 days after injection of 10(6) high M-CSF-expressing cells was 80%, significantly higher than that after injection of the mock-transfected cells, which killed all the mice by day 23. The survival rate appeared to depend on the amount of M-CSF produced. Moreover, all surviving mice after intravenous injection of the M-CSF-expressing sublines were rechallenged with 10(6) parental L1210 cells at day 50, and all survived up to day 100, demonstrating that M-CSF-expressing cells induced immune protection against the parental cells. The same improvement of survival was observed in mouse M-CSF-expressing cell lines. These observations imply that M-CSF cDNA is a candidate gene for use in gene therapy in leukemia.