Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1990 Mar;61(3):471–474. doi: 10.1038/bjc.1990.104

Recombinant interleukin-2 (rIL-2) with flavone acetic acid (FAA) in advanced malignant melanoma: immunological studies.

A K Ghosh 1, M Mellor 1, J Prendiville 1, N Thatcher 1
PMCID: PMC1971282  PMID: 2328217

Abstract

Natural killer (NK) cell activity and lymphokine activated killer (LAK) cell cytotoxicity were measured in patients receiving recombinant interleukin 2 (rIL-2) and flavone acetic acid (FAA) for treatment of progressing metastatic melanoma. NK activity was increased in 23 of 26 patients and LAK activity induced in 13 of 26 patients. However, levels of cytotoxicity in the present study were not significantly greater than a previous study using rIL-2 alone. LAK cell precursors demonstrated by in vitro incubation of pretreatment lymphocytes with IL-2 and subsequent cytotoxicity were no different in the patients compared to normal controls. Analysis of cell surface phenotypes failed to reveal any significant changes in the cell populations examined, including IL-2R and Leu 19. Although five patients had tumour response, one being complete, there was no correlation with the immunological parameters examined.

Full text

PDF
471

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anderson T. M., Ibayashi Y., Tokuda Y., Colquhoun S. D., Holmes E. C., Golub S. H. Effects of systemic recombinant interleukin-2 on natural killer and lymphokine activated killer activity of human tumor infiltrating lymphocytes. Cancer Res. 1988 Mar 1;48(5):1180–1183. [PubMed] [Google Scholar]
  2. Ching L. M., Baguley B. C. Induction of natural killer cell activity by the antitumour compound flavone acetic acid (NSC 347 512). Eur J Cancer Clin Oncol. 1987 Jul;23(7):1047–1050. doi: 10.1016/0277-5379(87)90357-9. [DOI] [PubMed] [Google Scholar]
  3. Cordell J. L., Falini B., Erber W. N., Ghosh A. K., Abdulaziz Z., MacDonald S., Pulford K. A., Stein H., Mason D. Y. Immunoenzymatic labeling of monoclonal antibodies using immune complexes of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP complexes). J Histochem Cytochem. 1984 Feb;32(2):219–229. doi: 10.1177/32.2.6198355. [DOI] [PubMed] [Google Scholar]
  4. Ettinghausen S. E., Lipford E. H., 3rd, Mulé J. J., Rosenberg S. A. Recombinant interleukin 2 stimulates in vivo proliferation of adoptively transferred lymphokine-activated killer (LAK) cells. J Immunol. 1985 Nov;135(5):3623–3635. [PubMed] [Google Scholar]
  5. Ettinghausen S. E., Lipford E. H., 3rd, Mulé J. J., Rosenberg S. A. Systemic administration of recombinant interleukin 2 stimulates in vivo lymphoid cell proliferation in tissues. J Immunol. 1985 Aug;135(2):1488–1497. [PubMed] [Google Scholar]
  6. Ferrini S., Moretta L., Pantaleo G., Moretta A. Surface markers of human lymphokine-activated killer cells and their precursors. Analysis at the population and clonal level. Int J Cancer. 1987 Jan 15;39(1):18–24. doi: 10.1002/ijc.2910390105. [DOI] [PubMed] [Google Scholar]
  7. Finlay G. J., Smith G. P., Fray L. M., Baguley B. C. Effect of flavone acetic acid on Lewis lung carcinoma: evidence for an indirect effect. J Natl Cancer Inst. 1988 Apr 20;80(4):241–245. doi: 10.1093/jnci/80.4.241. [DOI] [PubMed] [Google Scholar]
  8. Ghosh A. K., Dazzi H., Thatcher N., Moore M. Lack of correlation between peripheral blood lymphokine-activated killer (LAK) cell function and clinical response in patients with advanced malignant melanoma receiving recombinant interleukin 2. Int J Cancer. 1989 Mar 15;43(3):410–414. doi: 10.1002/ijc.2910430311. [DOI] [PubMed] [Google Scholar]
  9. Hank J. A., Kohler P. C., Weil-Hillman G., Rosenthal N., Moore K. H., Storer B., Minkoff D., Bradshaw J., Bechhofer R., Sondel P. M. In vivo induction of the lymphokine-activated killer phenomenon: interleukin 2-dependent human non-major histocompatibility complex-restricted cytotoxicity generated in vivo during administration of human recombinant interleukin 2. Cancer Res. 1988 Apr 1;48(7):1965–1971. [PubMed] [Google Scholar]
  10. Hornung R. L., Back T. C., Zaharko D. S., Urba W. J., Longo D. L., Wiltrout R. H. Augmentation of natural killer activity, induction of IFN and development tumor immunity during the successful treatment of established murine renal cancer using flavone acetic acid and IL-2. J Immunol. 1988 Nov 15;141(10):3671–3679. [PubMed] [Google Scholar]
  11. Hornung R. L., Young H. A., Urba W. J., Wiltrout R. H. Immunomodulation of natural killer cell activity by flavone acetic acid: occurrence via induction of interferon alpha/beta. J Natl Cancer Inst. 1988 Oct 5;80(15):1226–1231. doi: 10.1093/jnci/80.15.1226. [DOI] [PubMed] [Google Scholar]
  12. Itoh K., Tilden A. B., Kumagai K., Balch C. M. Leu-11+ lymphocytes with natural killer (NK) activity are precursors of recombinant interleukin 2 (rIL 2)-induced activated killer (AK) cells. J Immunol. 1985 Feb;134(2):802–807. [PubMed] [Google Scholar]
  13. McMannis J. D., Fisher R. I., Creekmore S. P., Braun D. P., Harris J. E., Ellis T. M. In vivo effects of recombinant IL-2. I. Isolation of circulating Leu-19+ lymphokine-activated killer effector cells from cancer patients receiving recombinant IL-2. J Immunol. 1988 Feb 15;140(4):1335–1340. [PubMed] [Google Scholar]
  14. Rosenberg S. A. Immunotherapy of cancer using interleukin 2: current status and future prospects. Immunol Today. 1988 Feb;9(2):58–62. doi: 10.1016/0167-5699(88)91261-3. [DOI] [PubMed] [Google Scholar]
  15. Rosenberg S. A., Lotze M. T., Muul L. M., Chang A. E., Avis F. P., Leitman S., Linehan W. M., Robertson C. N., Lee R. E., Rubin J. T. A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleukin-2 or high-dose interleukin-2 alone. N Engl J Med. 1987 Apr 9;316(15):889–897. doi: 10.1056/NEJM198704093161501. [DOI] [PubMed] [Google Scholar]
  16. Thatcher N., Dazzi H., Johnson R. J., Russell S., Ghosh A. K., Moore M., Chadwick G., Craig R. D. Recombinant interleukin-2 (rIL-2) given intrasplenically and intravenously for advanced malignant melanoma. A phase I and II study. Br J Cancer. 1989 Nov;60(5):770–774. doi: 10.1038/bjc.1989.357. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Urba W. J., Longo D. L., Lombardo F. A., Weiss R. B. Enhancement of natural killer activity in human peripheral blood by flavone acetic acid. J Natl Cancer Inst. 1988 Jun 1;80(7):521–525. doi: 10.1093/jnci/80.7.521. [DOI] [PubMed] [Google Scholar]
  18. West W. H., Tauer K. W., Yannelli J. R., Marshall G. D., Orr D. W., Thurman G. B., Oldham R. K. Constant-infusion recombinant interleukin-2 in adoptive immunotherapy of advanced cancer. N Engl J Med. 1987 Apr 9;316(15):898–905. doi: 10.1056/NEJM198704093161502. [DOI] [PubMed] [Google Scholar]
  19. Wiltrout R. H., Boyd M. R., Back T. C., Salup R. R., Arthur J. A., Hornung R. L. Flavone-8-acetic acid augments systemic natural killer cell activity and synergizes with IL-2 for treatment of murine renal cancer. J Immunol. 1988 May 1;140(9):3261–3265. [PubMed] [Google Scholar]
  20. Wiltrout R. H., Hornung R. L. Natural products as antitumor agents: direct versus indirect mechanisms of activity of flavonoids. J Natl Cancer Inst. 1988 Apr 20;80(4):220–222. doi: 10.1093/jnci/80.4.220. [DOI] [PubMed] [Google Scholar]
  21. Zaharko D. S., Grieshaber C. K., Plowman J., Cradock J. C. Therapeutic and pharmacokinetic relationships of flavone acetic acid: an agent with activity against solid tumors. Cancer Treat Rep. 1986 Dec;70(12):1415–1421. [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES