Abstract
We examined the antitumor effect of glycosylated recombinant lymphotoxin (LT) in combination with human interferon-gamma (IFN-gamma) on human tumors transplanted into nude mice and compared it with that of tumor necrosis factor (TNF). The results were as follows: (i) The systemic administration of glycosylated LT combined with IFN-gamma produced a significant antitumor activity against HT-1080 fibrosarcoma, G-361 malignant melanoma, KB nasopharyngeal carcinoma, and ZR-75-1 breast carcinoma, all of which are relatively resistant to a single treatment with LT or IFN-gamma. The synergistic effect was also seen in LT-sensitive HeLa S3 tumors. The effect was observed after either i.v. or s.c. injection. (ii) In contrast, no synergistic or additive effect on HeLa S3 tumors was observed in the case of TNF combined with IFN-gamma. (iii) The serum half-life of glycosylated LT in tumor-bearing mice was about 22-fold longer than that of TNF. In conclusion, glycosylated LT, especially in combination with IFN-gamma, appears to be a potent cytokine against tumor growth in vivo compared with TNF. Its long serum half-life can result in a strong antitumor effect in combination with IFN-gamma in vivo.
References
Jul 1, 1978·Cellular Immunology·G A GrangerJ C Hiserodt
Nov 8, 1985·Science·L J Old
Nov 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·J S PattonC Grunfeld
Sep 11, 1985·Nucleic Acids Research·G E NedwinP W Gray
Dec 19, 1985·Nature·B B AggarwalP E Hass
Nov 1, 1987·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·S E SalmonB Clark
Jan 1, 1986·International Journal of Immunopharmacology·Y SohmuraH Furuichi
Feb 1, 1973·Cellular Immunology·T W Williams, G A Granger
Oct 4, 1969·Nature·D C DumondeW T Howson
Sep 1, 1967·Science·N H Ruddle, B H Waksman
Jul 1, 1980·Proceedings of the National Academy of Sciences of the United States of America·T TaniguchiM Muramatsu
Jun 1, 1981·Proceedings of the National Academy of Sciences of the United States of America·T TaniguchiJ Vilcek
May 29, 1981·Biochemical and Biophysical Research Communications·D M WallaceS L Berger
Sep 1, 1983·Proceedings of the National Academy of Sciences of the United States of America·B D WilliamsonL J Old
Oct 28, 1982·Nature·D WallachM Revel
Dec 20, 1984·Nature·P W GrayL P Svedersky
Dec 20, 1984·Nature·D PennicaD V Goeddel
Mar 24, 1983·Nature·T TaniguchiJ Hamuro
Mar 1, 1984·The Journal of Experimental Medicine·D S Stone-WolffJ Vilcek
Feb 1, 1982·Proceedings of the Society for Experimental Biology and Medicine·A KhanJ M Hill
Mar 27, 1980·Nature·S NagataC Weissmann
Jan 1, 1981·Infection and Immunity·M R Ruff, G E Gifford
Mar 15, 1980·Cancer·B W PapermasterS J Buchok