In vitro and in vivo growth of B16F10 melanoma cells transfected with interleukin-4 cDNA and gene therapy with the transfectant.
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 decreased the tumorigenicity of B16F10 most strongly. We investigated whether gene therapy with IL-4-transfected B16F10 cells was possible. Flow-cytometric analysis showed that major histocompatibility complex class I and II expression in B16F10 and IL-4-cDNA-transfected B16F10 (B16F10-IL4) 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 sides. When 5 x 10(5) B16F10 cells were transplanted subcutaneously into the flanks of C57BL/6 mice, they all developed a tumor mass, whereas no tumor masses formed in those transplanted with B16F10-IL4 cells within 60 days. No nude, severe combined immunodeficient or beige mice were able to reject parental B16F10 or B16F10-IL4 cells, although, B16F10-IL4 tumor growth in all these immunodeficient mice was slower than that of B16F10. Therefore, we concluded that T and natural killer cells are necessary for rejection of B16F10-IL4 tumor cells.
Pharmacology Division, National Cancer Center Research Institute, Tokyo, Japan.
T
T
Ohira
Y
Y
Ohe
Y
Y
Heike
E R
ER
Podack
K J
KJ
Olsen
K
K
Nishio
M
M
Nishio
Y
Y
Miyahara
Y
Y
Funayama
H
H
Ogasawara
D000818:Animals; D002455:Cell Division / Q000502:physiology; D018076:DNA, Complementary / Q000235:genetics*; D005069:Evaluation Studies as Topic; D005260:Female; D015316:Genetic Therapy; D007153:Immunologic Deficiency Syndromes / Q000503:physiopathology; D007376:Interleukin-2 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics; D008297:Male; D008546:Melanoma, Experimental / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D014162:Transfection; D014407:Tumor Cells, Cultured; D014611:Vaccination
D018076:DNA, Complementary; D007376:Interleukin-2; D015850:Interleukin-6; D015847:Interleukin-4