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Tumor vaccination with macrophage colony-stimulating factor-producing Lewis
lung carcinoma in mice
T Morita, K Ikeda, M Douzono, M Yamada, F Kimura, K Kawakami, K Sasaki, K Motoyoshi, J Takahara and S Irino
Health Science Center, Kagawa University, Japan.
Expression of various cytokines by cytokine gene-transduced tumor cells has
been shown to increase antitumor immunity of tumor-bearing hosts. In the
present study, macrophage-colony stimulating factor (M-CSF) cDNA was
retrovirally transfected into Lewis lung carcinoma cells (3LL) of C57BL/6
mouse origin, and the effects of M-CSF expression were studied by
inoculating syngeneic C57BL/6 mice with M-CSF-expressing 3LL cells. The
mice inoculated with the lowest M-CSF-producing 3LL clone showed
significant prolongation of the survival compared with wild-type 3LL-
Inoculated mice, and 70% or more of the mice inoculated with 3LL clones
with higher M-CSF production rejected inoculation. Mice injected with
radiation-inactivated M-CSF-expressing 3LL cells before or after
Inoculation of wild-type 3LL cells showed prolonged survival compared with
mice injected with radiated control 3LL cells before or after
transplantation of wild-type cells. In vivo depletion of effector
subpopulations by injection of antibodies against CD4+ T cells, CD8+ T
cells, or natural killer (NK) cells suggested involvement of NK cells and
CD4+ T cells in M-CSF-mediated antitumor cytotoxicity in M-CSF- producing
3LL cells-inoculated mice. Severe combined immunodeficiency (SCID) mice
with defective T- and B-cell function showed prolonged survival duration
after inoculation with M-CSF-expressing 3LL cells compared with those
transplanted with control 3LL cells, and this effect of M-CSF expression by
3LL-cells in SCID mice was also abolished by in vivo depletion of NK cells
by antibody injection. These findings together with the previous reports
that M-CSF augments antibody- dependent and-independent antitumor
cytotoxicity suggest that M-CSF induces tumor immunity in this
cytokine-expressing tumor- transplantation model.
Volume 88,
Issue 3,
pp. 955-961,
08/01/1996
Copyright © 1996 by The American Society of Hematology
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