T. Ohira et al., IN-VITRO AND IN-VIVO GROWTH OF B16F10 MELANOMA-CELLS TRANSFECTED WITHINTERLEUKIN-4 CDNA AND GENE-THERAPY WITH THE TRANSFECTANT, Journal of cancer research and clinical oncology, 120(11), 1994, pp. 631-635
In an attempt to develop the most effective cytokine gene therapy, we
transfected mouse interleukin(IL)-2, mouse IL-4, and human IL-6 cDNAs
into mouse melanoma cells, B16F10. Transfection with IL-4 cDNA decreas
ed the tumorigenicity of B16F10 most strongly. We investigated whether
gene therapy with IL-4-transfected B16F10 cells was possible. Flowcyt
ometric analysis showed that major histocompatibility complex class I
and II expression in B16F10 and IL-4-cDNA-transfected B16F10(B16F10-IL
4) cells did not differ. Doubling times of B16F10 and B16F10-IL4 were
20.1 and 21.1 h respectively. The growth of B16F10 cells was retarded
if C57BL/6 mice were inoculated with B16F10-IL4 at the contralateral s
ides. When 5 x 10(5) B16F10 cells were transplanted subcutaneously int
o the flanks of C57BL/6 mice, they all developed a tumor mass, whereas
no tumor masses formed in those transplanted with B16F10-IL4 cells wi
thin 60 days. No nude, severe combined immunodeficient or beige mice w
ere able to reject parental B16F10 or B16F10-IL4 cells, although, B16F
10-IL4 tumor growth in all these immunodeficient mice was slower than
that of B16F10. Therefore, we concluded that T and natural killer cell
s are necessary for rejection of B16F10-IL4 tumor cells.