Synergistic antitumor effect of glycosylated recombinant human lymphotoxin with human interferon-gamma on lymphotoxin-sensitive human tumor.
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.
Kawatsu
M
M
Biochemical Research Laboratories, Kanegafuchi Chemical Industry Co., Takasago, Japan.
Funahashi
I
I
Kajikawa
T
T
Takeo
K
K
Asahi
T
T
Yamashita
T
T
Kawaharada
H
H
Watanabe
K
K
D000595:Amino Acid Sequence; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D004357:Drug Synergism; D006031:Glycosylation; D006207:Half-Life; D006367:HeLa Cells; D006801:Humans; D007371:Interferon-gamma / Q000627:therapeutic use*; D008233:Lymphotoxin-alpha / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009368:Neoplasm Transplantation; D011994:Recombinant Proteins / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000493:pharmacokinetics / Q000627:therapeutic use
D008233:Lymphotoxin-alpha; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma