Augmentation of antitumor immunity using genetically M-CSF-expressing L1210 cells.
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.
Kimura
F
F
The Third Department of Internal Medicine, National Defense Medical College, Saitama, Japan.
Douzono
M
M
Ohta
J
J
Morita
T
T
Ikeda
K
K
Nakamura
Y
Y
Sato
K
K
Yamada
M
M
Nagata
N
N
Motoyoshi
K
K
D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects; D018076:DNA, Complementary / Q000235:genetics; D015316:Genetic Therapy; D006801:Humans; D007111:Immunity, Cellular; D007939:Leukemia L1210 / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008221:Lymphoid Tissue / Q000473:pathology; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D008264:Macrophages / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009368:Neoplasm Transplantation; D017382:Reactive Oxygen Species / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; D017382:Reactive Oxygen Species; D011993:Recombinant Fusion Proteins; D016173:Macrophage Colony-Stimulating Factor