Summary
A comparative study of the antitumor effect of murine recombinant interferon(β) 〈Mu-rIFN(β)〉 and murine recombinant interferon(γ) 〈Mu-rIFN(γ)〉 on B16-F10 melanoma was conducted. Administration of Mu-rIFN(γ) i.p. into C57BL/6 mice on days 1 to 7 produced a higher suppressive effect than Mu-rIFN(β) both on the growth of s.c. implanted tumor and on the formation of artificial pulmonary metastasis. Pharmacokinetic study of Mu-rIFN(γ) demonstrated that high plasma levels were retained for a long time. In clonogenic assay, Mu-rIFN(γ) at 1000 units/ml showed about 80% inhibition of colonies of B16-F10 melanoma. However, Mu-rIFN(β) hardly inhibited the colonies, even at 1000 units/ml. Augmentation of natural killer (NK) cytotoxicity was much greater with Mu-rIFN(β) than Mu-rIFN(γ), whereas Mu-rIFN(γ) enhanced the cytotoxicity of peritoneal macrophages more strongly than Mu-rIFN(β). Injection of Mu-rIFN(γ) i.p. 1 day before tumor challenge also inhibited the formation of pulmonary metastasis of B16-F10 melanoma. However, pretreatment of mice with carrageenan significantly suppressed the inhibitory effect of Mu-rIFN(γ). From these results, it is suggested that the inhibitory effect of Mu-rIFN(γ) on the tumor growth and metastases of B16-F10 melanoma is mediated partly by direct antitumor effect and partly by the activation of macrophages, and that the augmentation of NK activity contributes mainly to the antitumor effect of Mu-rIFN(β).
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References
Armstrong JA (1981) Cytopathic effect inhibition assay for interferon: microculture plate assay. In: Methods in enzymology, vol 78. Academic Press, New York, pp 381
Belardelli F, Gresser I, Maury C, Maunoury MT (1982) I. Antitumor effects of interferon in mice injected with interferon-sensitive and interferon-resistant Friend leukemia cells. Int J Cancer 30:813
Belardelli F, Gresser I, Maury C, Maunoury MT (1982) Antitumor effects of interferon in mice injected with interferon-sensitive and interferon-resistant Friend leukemia cells. II. Role of host mechanisms. Int J Cancer 30:821
Belardelli F, Gresser I, Maury C, Duvillard P, Prade M, Maunoury MT (1983) Antitumor effects of interferon in mice injected with interferon-sensitive and interferon-resistant Friend leukemia cells. III. Inhibition of growth and necrosis of tumors implanted subcutaneously. Int J Cancer 31:649
Blalock JE, Georgiades JA, Langford MP, Johnson HM (1980) Purified human immune interferon has more potent anticellular activity than fibroblast or leukocyte interferon. Cell Immunol 49:390
Czarniecki CW, Fennie CW, Powers DB, Estell DA (1984) Synergistic antiviral and antiproliferative activities of Escherichia coli-derived human alpha, beta, and gamma interferons. J Virol 49:490
De Clercq E, Zhang ZX, Huygen K, Leyten R (1982) Inhibitory effect of interferon on the growth of spontaneous mammary tumors in mice. J Natl Cancer Inst 69:653
De Maeyer-Guignard J, De Maeyer E (1985) Immunomodulation by interferons: recent developments. In: Gresser I (ed) Interferon, vol 6. Academic Press, New York, pp 69
Djeu JY, Heinbaugh JA, Holden HT, Herberman RB (1979) Role of macrophages in the augmentation of mouse natural killer cell activity by poly I: C and interferon. J Immunol 122:182
Fidler IJ (1973) Selection of successive tumor lines for metastasis. Nature 242:148
Fidler IJ, Barnes Z, Fogler WE, Kirsh R, Bugelski P, Poste G (1982) Involvement of macrophages in the eradication of established metastasis following intravenous injection of liposomes containing macrophage activators. Cancer Res 42:496
Gresser I, Maury C, Brouty-Boye D (1972) Mechanism of the antitumor effects of interferon in mice. Nature 239:167
Herberman RB, Ortaldo JR (1981) Natural killer cells: their role in defenses against disease. Science 214:24
Ishizuka S, Otani S, Morisawa S (1977) Effects of carrageenan on immune responses. I. Studies on the macrophage dependency of various antigens after treatment with carrageenan. J Immunol 118:1213
Kataoka T, Oh-hashi F, Sakurai Y, Usui K, Ida N (1984) Relative contribution of antiproliferative and host immunity-associated activity of mouse interferon in murine tumor therapy. Cancer Res 44:5661
Lee SH, Chiu H, Rinderknecht E, Sabo W, Stebbing N (1983) Importance of treatment regimen of interferon as an antitumor agent. Cancer Res 43:4172
Lin SL, Greene JJ, Ts'o POP, Carter WA (1982) Sensitivity and resistance of human tumor cells to interferon and rI rC. Nature 297:417
Sakurai M, Iigo M, Ozaki A, Jett JR, Sasaki Y, Hoshi A, Saijo N (1986) Inhibitory effect of murine recombinant interferon(β) on the pulmonary metastasis of B-16 melanoma. Jpn J Cancer Res (Gann) 77:774
Shalaby MR, Weck PK, Rinderknecht E, Harkins RN (1984) Effects of bacteria-produced human alpha, beta, and gamma interferons on in vitro immune function. Cell Immunol 84:380
Schiller JH, Groveman DS, Schmid SM, Willson JK, Cummings KB, Borden EC (1986) Synergistic antiproliferative effect of human recombinant 54-α or βser-interferon with γ-interferon on human cell lines of various histogenesis. Cancer Res 46:483
Uno K, Shimizu S, Ido M, Naito K, Inaba K, Oku T, Kishida T, Muramatsu S (1985) Direct and indirect effects of interferon on in vivo murine tumor cell growth. Cancer Res 45:1320
Varesio L, Blasi E, Thurman GB, Talmadge JE, Wiltrout RH, Herberman RB (1984) Potent activation of mouse macrophages by recombinant interferon-γ. Cancer Res 44:4465
Vilcek J, Kelke HC, Jumming LE, Yip YK (1985) Structure and function of human interferon gamma. In: Ford RJ (ed) Mediators of cell growth and differentiation. Raven Press, New York, pp 299
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Sakurai, M., Iigo, M., Tamura, T. et al. Comparative study of the antitumor effect of two types of murine recombinant interferons, (β) and (γ), against B16-F10 melanoma. Cancer Immunol Immunother 26, 109–113 (1988). https://doi.org/10.1007/BF00205602
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DOI: https://doi.org/10.1007/BF00205602