Log in

Evaluation of natural killer and lymphokine-activated killer (LAK) cell activity in vivo in patients treated with high-dose interleukin-2 and adoptive transfer of autologous LAK cells

  • Original Papers
  • Clinical Oncology
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Summary

This study investigated the development of peripheral blood natural killer (NK) and lymphokineactivated killer (LAK) cell activity in vivo in cancer patients treated with high doses of recombinant interleukin-2 and autologous LAK cell infusion. It was found that interleukin-2 administration by bolus injection resulted in an early but transient rise of NK and LAK cell activity in vivo during the first 5–9 days of treatment (postpriming period), whereas continuous infusion of interleukin-2 caused an increase in both cytotoxic activities in the second phase of the treatment, concomitant with infusions of autologous LAK cells. Elevated NK but not LAK cell activity in vivo in the continuous-infusion patients persisted up to 180 days after completion of therapy. In both bolus and continuous interleukin-2 protocols, augmented NK cell activity in vivo appeared to be correlated with a beneficial response to therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Germany)

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Atkins MB, Gould JA, Allegretta M, Li JJ, Dempsey RA, Rudders RA, Parkinson DR, Reichlin S, Mier JW (1986) Phase I evaluation of recombinant interleukin-2 in patients with advanced malignant disease. J Clin Oncol 4:1380–1391

    Google Scholar 

  • Boldt DH, Mills BJ, Gemlo BT, Holden H, Mier J, Paietta E, McMannis JD, Escobedo LV, Sniecinski I, Rayner AA, Hawkins MJ, Atkins MB, Ciobanu N, Ellis TM (1988) Laboratory correlates of adoptive immunotherapy with recombinant interleukin-2 and lymphokine-activated killer cells in humans. Cancer Res 48:4409–4416

    Google Scholar 

  • Ettinghausen SE, Moore JG, White DE, Platanias L, Young NS, Rosenberg SA (1987) Hematologic effects of immunotherapy with lymphokine-activated killer cells and recombinant interleukin-2 in cancer patients. Blood 69:1654–1660

    Google Scholar 

  • Fauci AS, Rosenberg SA, Sherwin SA, Dinarello CA, Longo DL, Lane HC (1987) Immunomodulators in clinical medicine. Ann Intern Med 106:421–433

    Google Scholar 

  • Hank JA, Kohler PC, Weil-Hillman G, Rosenthal N, Moore KH, Storer B, Minkoff D, Bradshaw J, Bechhofer R, Sondel PM (1988) 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 48:1965–1971

    Google Scholar 

  • Harel W, Shau H, Hadley C, Stahlberg J, Reisfeld R, Cheresh D, Mitchell M (1988) Immunological effects of therapy with low dose cyclophosphamide and recombinant interleukin-2. Proc Am Assoc Cancer Res 29:401

    Google Scholar 

  • Ibayashi Y, Tokuda Y, Saks ER, Sarna GR, Golub SH (1987) In vivo and in vitro activation of NK cytotoxicity with IL-2. In: Truitt RL, Gale RP, Bortin MM (eds) Cellular immunotherapy of cancer. Alan Liss, New York, pp 275–285

    Google Scholar 

  • Lotze MT, Matory YL, Ettinghausen SE, Rayner AA, Sharrow SO, Scipp CAY, Custer MC, Rosenberg SA (1985) In vivo administration of purified human interleukin-2, II. Half life, immunologic effects, and expansion of peripheral lymphoid cells in vivo with recombinant IL 2. J Immunol 135:2865–2875

    Google Scholar 

  • McMannis JD, Fisher RI, Creekmore SP, Braun DP, Harris JE, Ellis TM (1988) 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 140:1335–1340

    Google Scholar 

  • Mitchell MS, Foon K, Watman N, Kmack A, Bradley E, Rudolph A, Poiesz B, Zamkoff K (1988) Biology of IL-2 and related lymphokines. Regulation of peripheral blood lymphokine activated killer cell activity. Immunol Allergy Clin North Am 8:131–133

    Google Scholar 

  • Paciucci PA, Konefal RG, Ryder R, Bekesi GJ, Glidewell O, Holland JF (1988) In vitro modification of the immune response induced by therapy with recombinant interleukin-2. Proc Am Assoc Cancer Res 29:407

    Google Scholar 

  • Phillips JH, Gemlo BT, Myers WW, Rayner AA, Lanier LL (1987) In vivo and in vitro activation of natural killer cells in advanced cancer patients undergoing combined recombinant interleukin 2 and LAK cell therapy. J Clin Oncol 5:1933–1941

    Google Scholar 

  • Pross HF, Maroun JA (1984) The standardization of NK cell assays for use in studies of biological response modifiers. J Immunol Methods 68:235–249

    Google Scholar 

  • Pross HF, Baines MG, Rubin P, Shragge P, Patterson MS (1981) Spontaneous human lymphocyte-mediated cytotoxicity against tumor target cells. IX. The quantitation of natural killer cell activity. J Clin Immunol 1:51–63

    Google Scholar 

  • Rosenberg SA (1988) Immunotherapy of patients with advanced cancer using interleukin-2 alone or in combination with lymphokine activated killer cells. In: DeVita VT, Hellman S, Rosenberg SA (eds) Important advances in oncology. JB Lippincott, Philadelphia, pp 217–257

    Google Scholar 

  • Sano T, Sajio N, Sasaki Y, Shinkai T, Eguchi K, Tamura T, Sakurai M, Takahashi H, Nakano H, Nagakawa K, Hong WS (1988) Three schedules of recombinant human interleukin-2 in the treatment of malignancy: side effects and immunologic effects in relation to serum level. Jpn J Cancer Res 79:131–143

    Google Scholar 

  • Thompson JA, Lee DJ, Lindgren CG, Benz LA, Collins C, Levitt D, Fefer A (1988) Influence of dose and duration of infusion of interleukin-2 on toxicity and immunomodulation. J Clin Oncol 6:669–678

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Supported by the US-Poland Cancer Program (NCI) and by NCI Contract NO1-CM-73705

Rights and permissions

Reprints and permissions

About this article

Cite this article

Walewski, J., Paietta, E., Dutcher, J. et al. Evaluation of natural killer and lymphokine-activated killer (LAK) cell activity in vivo in patients treated with high-dose interleukin-2 and adoptive transfer of autologous LAK cells. J Cancer Res Clin Oncol 115, 170–174 (1989). https://doi.org/10.1007/BF00397919

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00397919

Key words

Navigation