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In vitro and in vivo growth of B16F10 melanoma cells transfected with interleukin-4 cDNA and gene therapy with the transfectant

  • Original Papers
  • Experimental Oncology
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Abstract

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. Flowcytometric 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 5×105 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.

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Abbreviations

IL:

interleukin

LLC:

Lewis lung Carcinoma

SCID:

severe combined immuno deficient

LAK:

lymphokine-activated killer

NK:

natural killer

G-CSF:

granulocyte-colony-stimulating factor

References

  • Blankenstein T, Qin Z, Überla K, Müller W, Rosen H, Volk H-D, Diamantstein T (1991) Tumor suppression after tumor cell-targeted tumor necrosis factor α gene transfer. J Exp Med 173:1047–1052

    Google Scholar 

  • Bruggen PVD, Traversari C, Chomez P, Lurquin C, Plaen ED, Eynde BVD, Knuth A, Boon T (1991) A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science 254:1643–1647

    Google Scholar 

  • Colombo MP, Ferrari G, Stoppacciaro A, Parenza M, Rodolfo M, Mavilio F, Parmiani G (1991) Granulocyte colony-stimulating factor gene transfer suppresses tumorigencity of a murine adenocarcinoma. J Exp Med 173:889–897

    Google Scholar 

  • Crawford RM, Finbloom DS, Ohara J, Paul WE, Meltzer MS (1987) B cell stimulatory factor-1 (interleukin 4) activates macrophages for increased tumoricidal activity and expression of Ia antigens. J Immunol 139:135–141

    Google Scholar 

  • Dranoff G, Jaffee E, Lazenby A, Golumbek P, Levitsky H, Brose K, Jackson V, Hamada H, Pardoll DM, Mulligan RC (1993) Vaccination with irradiated with tumor cells engineered to secrete murine granulocyte-macrophage colony stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity. Proc Natl Acad Sci USA 90:3539–3543

    Google Scholar 

  • Fearon ER, Pardoll DM, Itaya T, Golumbek P, Levitsky HI, Simons JW, Karasuyama H, Vogelstein B, Frost P (1990) Interleukin-2 production by tumor cell bypasses T helper function in the generation of an antitumor response. Cell 60:397–403

    Google Scholar 

  • Felgner PL, Gadek TR, Holn M, Roman R, Chan HW, Wenz M, Northrop JP, Ringold GM, Danielsen M, (1987) Lipofection: a highly efficient, lipid-mediated DNA-transfection procedure. Proc Natl Acad Sci USA 84:7413–7417

    Google Scholar 

  • Gansbacher B, Bannerji R, Daniels B, Zier K, Cronin K, Gilboa E (1990a) Retroviral vector-mediated γ-interferon gene transfer into tumor cells generates potent and long lasting antitumor immunity. Cancer Res 50:7820–7825

    Google Scholar 

  • Gansbacher B, Zier K, Daniels B, Cronin K, Bannerji R, Gilboa E (1990b) Interleukin 2 gene transfer into tumor cells abrogates tumorigenicity and induces protective immunity. J Exp Med 172:1217–1224

    Google Scholar 

  • Golumbek PT, Lazenby AJ, Levitszky HI, Jaaffee LM, Karasuyama H, Baker M, Pardoll DM (1991) Treatment of established renal cancer by tumor cells engineered to secrete interleukin-4. Science 254:713–716

    Google Scholar 

  • Hock H, Dorsch M, Diamantstein T, Blankenstein T (1991) Interleukin 7 induces CD4+ T cell-dependent and tumor rejection. J Exp Med 174:1291–1298

    Google Scholar 

  • Howard M, Farrar J, Hilfiker M, Johnson B, Takatsu K, Homaoka T, Paul WE (1982) Identification of a T cell-derived B cell growth factor distinct from interleukin 2. J Exp Med 155:914–923

    Google Scholar 

  • Karasuyama H, Melchers F (1988) Establishment of mouse cell lines which constitutively secrete large quantities of interleukin 2, 3, 4 or 5, using modified cDNA expression vectors. Eur J Immunol 18:97–104

    Google Scholar 

  • Lutzker S, Rothman P, Pollock R, Coffman R, Alt FW (1988) Mitogen-and IL-4-regulated expression of germ-line Ig γ2b transcripts: evidence for directed heavy chain class switching. Cell 53:177–184

    Google Scholar 

  • Mizuno M, Yoshida J, Sugita K, Inoue I, Seo H, Hayashi Y, Koshizaka T, Yagi K (1990) Growth inhibition of glioma cells transfected with the human β-interferon gene by liposomes coupled with a monoclonal antibody. Cancer Res 50:7826–7829

    Google Scholar 

  • Mosmann TR, Bond MW, Coffman RL, Ohara J, Paul WE (1986) T-cell and mast cell lines respond to B-cell stimulatory factor 1. Proc Natl Acad Sci USA 83:5654–5658

    Google Scholar 

  • Mulé JJ, Smith CA, Rosenberg SA (1987) Interleukin 4 (B cell stimulatory factor 1) can mediate the induction of lymphokine-activated killer cell activity directed against fresh tumor cells. J Exp Med 166:792–797

    Google Scholar 

  • Noelle R, Krammer PH, Ohara J, Uhr JW, Vitetta ES (1984) Increased expression of Ia antigens on resting B cells: An additional role for B-cell growth factor. Proc Natl Acad Sci USA 81:6149–6153

    Google Scholar 

  • Ohe Y, Podack ER, Olsen KJ, Miyahara Y, Ohira T, Miura K, Nishio K Saijo N (1993a) Combination effect of vaccination with IL2 and IL4 cDNA transfected cells on the induction of a therapeutic immune response against Lewis lung carcinoma cells. Int J Cancer 53:432–437

    Google Scholar 

  • Ohe Y, Podack ER, Olsen KJ, Miyahara Y, Saito H, Koishihara Y, Ohsugi Y, Ohira T, Saijo N (1993b) Interleukin-6 cDNA transfected Lewis lung carcinoma cells show unaltered net tumor growth rate but cause weight loss and shorten survival in syngenic mice. Br J Cancer 67:939–944

    Google Scholar 

  • Porgador A, Gansbacher B, Bannerji R, Tzehoval E, Gilboa E, Feldman M, Eisenbach L (1993) Anti-metastic vaccination of tumorbearing mice with IL-2-gene-inserted tumor cells. Int J Cancer 53:471–477

    Google Scholar 

  • Roehm NW, Leibson HJ, Zlothik A, Kappler J, Marrack P, Cambier JC (1984) Interleukin-induced increase in Ia expression by normal mouse B cells. J Exp Med 160:679–694

    Google Scholar 

  • Snapper CM, Paul WE (1987) B cell stimulatory factor-1 (interleukin 4) prepares resting murine B cells to secrete IgG1 upon subsequent stimulation with bacterial lipolysaccharide. J Immunol 139:10–17

    Google Scholar 

  • Sun WH, Kresle RA, Phillips AW, Ershler WB (1992) In vivo and in vitro characteristics of interleukin 6-transfected B16 melanoma cells. Cancer Res 52:5412–5415

    Google Scholar 

  • Teng MN, Park BH, Koeppen HKW, Tracey KJ, Fendly BM, Schreiber H (1991) Long-term inhibition of tumor growth by tumor necrosis factor in the absence of cachexia or T cell immunity. Proc Natl Acad Sci USA 88:3535–3539

    Google Scholar 

  • Tepper RI, Pattengale PK, Leder P (1989) Murine interleukin-4 displays potent anti-tumor activity in vivo. Cell 57:503–512

    Google Scholar 

  • Watanabe Y, Kuribayashi K, Miyake S, Nishihara K, Nakayama E, Taniyama T, Sakata T (1989) Exogenous expression of mouse interferon γ cDNA in mouse neuroblastoma C1300 cells results in reduced tumorigenicity by augmented anti-tumor immunity. Proc Natl Acad Sci USA 86:9456–9460

    Google Scholar 

  • Widmer MB, Grabstein KH (1987) Regulation of cytolytic T-lymphocyte generation by B-cell stimulatory factor. Nature 326:795–798

    Google Scholar 

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Ohira, T., Ohe, Y., Heike, Y. et al. In vitro and in vivo growth of B16F10 melanoma cells transfected with interleukin-4 cDNA and gene therapy with the transfectant. J Cancer Res Clin Oncol 120, 631–635 (1994). https://doi.org/10.1007/BF01245372

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  • DOI: https://doi.org/10.1007/BF01245372

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