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Lack of effects of recombinant human interleukin-4 onin vitro colony formation of freshly explanted human tumor cells

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Summary

Interleukin-4 is a highly pleiotropic T-cell derived lymphokine that has been reported to stimulate a host cell-mediated antitumor response. Recombinant human interleukin-4 (rhuIL-4) is currently undergoing clinical phase I trials. We have studied the growth modulating effects of rhuIL-4 on a variety of freshly explanted human tumor specimens using anin vitro soft agar cloning system. Final concentrations of 0.1 to 10 ng/ml were used in continuous incubation experiments. Of 147 specimens, 73 (50%) were evaluable for the determination of tumor growth modulating activity. The most common tumor types recruited included breast, nonsmall cell lung, ovarian cancer and melanoma. Stimulation of tumor colony forming units (colony formation ≥1.5× controls) was observed in 0/73 tumors. Similarly, only 1/73 (1.3%) specimens (a non-small cell lung cancer) had a significant decrease in tumor colony forming units (colony formation ≤ 0.5× controls) at 1 ng/ml. We conclude that rhuIL-4 is not a direct modulator of tumor colony formationin vitro. However, antitumor effects could perhaps be achievedin vivo via the immune-modulating effects of Interleukin-4.

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References

  1. Paul WE: Interleukin-4: a prototypic immunoregulatory lymphokine. Blood 77:1859–1870, 1991

    Google Scholar 

  2. Jansen JH, Fibbe WE, Willemze R, Kluin-Nelemans JC: Interleukin-4, A regulatory protein. Blut 60:269–274, 1990

    Google Scholar 

  3. Ohara J: Interleukin-4: molecular structure and biochemical characteristics, biological function, and receptor expression. Year Immunol 5:126–159, 1989

    Google Scholar 

  4. Paul WE, Ohara J: B-cell stimulatory factor-1/interleukin-4. Annu Rev Immunol 5:429–459, 1987

    Google Scholar 

  5. Peschel C, Paul WE, Ohara J, Green I: Effects of B cell stimulating factor-1/interleukin 4 on hematpoietic progenitor cells. Blood 70:254–263, 1987

    Google Scholar 

  6. Rennick D, Yang G, Muller-Sieburg C, Smith C, Arai N, Takebe Y, Gemmel L: Interleukin 4 (B-cell stimulatory factor 1) can enhance or antagonize the factor-dependent growth of hematopoietic progenitor cells. Proc Natl Acad Science USA 84:6889–6893, 1987

    Google Scholar 

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

    Google Scholar 

  8. Spits H, Yssel H, Takebe Y, Arai N, Yokota T, Lee F, Arai KL, Banchereau J, De Vries JE: Recombinant interleukin 4 promotes the growth of human T cells. J Immunol 139:1142–1147, 1987

    Google Scholar 

  9. Le HV, Ramanathan L, Labdon JE, Mays-Ichinco CA, Syto R, Arai N, Hoy P, Takebe Y, Nagabhushan TL, Trotta PP: Isolation and characterization of multiple variants of recombinant human interleukin 4 expressed in mammalian cells. J Biol Chem 263:10817–10823, 1988

    Google Scholar 

  10. Windsor WT, Syto R, Le HV, Trotta PP: Analysis of the conformation and stability of escherichia coli derived recombinant human interleukin 4 by circular dichroism. Biochem 30:1259–1264, 1991

    Google Scholar 

  11. Van Kimmenade A, Bond MW, Schumacher JH, Laquoi C, Kastelein RA: Expression, renaturation and purification of recombinant human interleukin 4 from Escherichia coli. Eur J Biochem 173:109–14, 1988

    Google Scholar 

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

    Google Scholar 

  13. Taylor CW, Grogan TM, Salmon SE: Effects of interleukin-4 on thein vitro growth of human lymphoid and plasma cell neoplasms. Blood 75:1114–1118, 1990

    Google Scholar 

  14. Ohnishi K, Ichikawa A, Kagami Y, Nagasaka T, Niwa T, Hotta T, Saito H: Interleukin 4 and gamma-interferon may play a role in the histopathogenesis of peripheral T-cell lymphoma. Cancer Res 50:8028–8033, 1991

    Google Scholar 

  15. O'Garra A, Barbis D, Wu J, Hodgkin PD, Abrams J, Howard M: The BCL1 B lymphoma responds to IL-4, IL-5, and GM-CSF. Cell Immunol 123:189–200, 1989

    Google Scholar 

  16. Oelke M, De Riese W, Raab H-R, Meyer H-J, Neukam D, Hanauske U, Freund M, Poliwoda H, Rastetter J, Hanauske A-R: Effects of IL-4, IL-5, and IL-7 on clonogenic growth of primary human tumorsin vitro (abstract). Ann Hematol 62:A104, 1991

    Google Scholar 

  17. Yokota T, Otsuka T, Mosmann T, Banchereau J, Defrance T, Blanchard D, DeVries JE, Lee F, Arai K: Isolation and characterization of a human interleukin cDNA clone, homologous to mouse B-cell stimulating factor 1, that express B-cell and T-cell-stimulating activities. Proc Natl Acad Science USA 83:5894–5898, 1986

    Google Scholar 

  18. Hamburger AW, Salmon SE: Primary bioassay of human tumor stem cells. Science 197:461–463, 1977

    Google Scholar 

  19. Hanauske U, Hanauske A-R, Marshall MH, Muggia VA, Von Hoff DD: Biphasic effects of vanadium salts onin vitro tumor colony growth. Int J Cell Cloning 5:170–178, 1987

    Google Scholar 

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

    Google Scholar 

  21. Defrance T, Vandervliet B, Pene J, Banchereau J: Human recombinant IL-4 induces activated B lymphocytes to produce IgG and IgM. J Immunol 141:2000–2005, 1988

    Google Scholar 

  22. Te Velde AA, Klomp JPG, Yard BA, De Vries JE, Figdor CG: Modulation of phenotypic and functional properties of human peripheral blood monocytes by IL-4. J Immunol 140:1548–1554, 1988

    Google Scholar 

  23. Boey H, Rosenbaum R, Costracan J, Borish L: Interleukin-4 is a neutrophil activator. J Allergy Clin Immunol 83:978–986, 1989

    Google Scholar 

  24. Wersall P, Masucci G, Mellstedt H: Interleukin-4 augments the cytotoxic capacity of lymphocytes and monocytes in antibody-dependent cellular cytotoxicity. Cancer Immunol Immunother 33:45–49, 1991

    Google Scholar 

  25. Totpal K, Aggarwal BB: Interleukin 4 potentiates the antiproliferative effects of tumor necrosis factor in various tumor cell lines. Cancer Res 51:4266–4270, 1991

    Google Scholar 

  26. Hoon DSB, Banez M, Okun E, Morton DL, Irie RF: Modulation of human melanoma cells by interleukin-4 and in combination with gamma-interferon orα-tumor necrosis factor. Cancer Res 51:2002–2008, 1991

    Google Scholar 

  27. Toi M, Bicknell R, Harris AL: Inhibition of colon and breast carcinoma cell growth by interleukin-4. Cancer Res 52:275–279, 1992

    Google Scholar 

  28. Tungekar MF, Turley H, Dunnill MS, Gatter KC, Ritter MA, Harris AL: Interleukin 4 receptor expression on human lung tumors and normal lung. Cancer Res 51:261–264, 1991

    Google Scholar 

  29. Tepper RI, Pattengale PK, Leder P: Murine interleukin-4 displays potent anti-tumor activityin vivo. Cell 57:503–512, 1989

    Google Scholar 

  30. Bosco M, Giovarelli M, Forni M, Modesti A, Scarpa S, Masuelli L, Forni G: Low doses of IL-4 injected perilymphatically in tumor-bearing mice inhibit the growth of poorly and apparently non-immunogenic tumors and induce a tumor-specific memory. J Immunol 145:3136–3140, 1990

    Google Scholar 

  31. Hanauske A-R, Hanauske U, Von Hoff DD: The human tumor cloning assay in cancer research and therapy. Curr Probl Cancer 9:1–50, 1985

    Google Scholar 

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Hanauske, A.R., Degen, D., Marshall, M.H. et al. Lack of effects of recombinant human interleukin-4 onin vitro colony formation of freshly explanted human tumor cells. Invest New Drugs 10, 269–273 (1992). https://doi.org/10.1007/BF00944180

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