Advertisement

Interleukin-2 and lymphokine activated killer (LAK) cells

  • Sylvie Negrier
  • Thierry O. Philip

Abstract

Lymphokine-activated-killer cells are peripheral lymphocytes that develop, following exposure to Interleukin-2 (IL2), the ability to lyse tumour cells but not normal cells. This phenomenon has been extensively studied in the early eighties. These LAK cells appeared cytotoxic to non-cultured, natural killer-cell-resistant tumour cells without antigenic stimulation implicating killing in a non MHC-restricted manner [1, 2]. Extensive studies of the precursors of LAK cells have revealed that they are constituted in part of activated cytotoxic T cells but consist predominantly of activated Natural-Killer (NK) cells [3,4].

Keywords

Clin Oncol Killer Cell Metastatic Renal Cell Carcinoma Activate Killer Cell Adoptive Immunotherapy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Grimm EA, Mazumder A, Zhang HZ, Rosenberg SA. Lymphokine activated killer cell phenomenom. J Exp Med 1982; 155: 1823–41.PubMedCrossRefGoogle Scholar
  2. 2.
    Rosenstein M, Yron I, Kaufmann Y, Rosenberg SA Lymphocyte activated killer cells: lysis of fresh syngeneic natural killer-resistant murine tumor cells by lymphocytes cultured in Interleukin 2. Cancer Res 1984; 44: 1946–53PubMedGoogle Scholar
  3. 3.
    Grimm EA, Ramsey KM, Mazumder A, et al. Lymphokine-activated killer cell phenomenom. II Precursor phenotype is biologically distinct from peripheral T. lymphocytes, memory cytotoxic thymus-derived lymphocytes, and natural killer cells. J Exp Med 1983; 157: 884–97.PubMedCrossRefGoogle Scholar
  4. 4.
    Philips JH, Lanier LL. Dissection of the lymphokine-activated killer phenomenom. Relative contribution of peripheral bolld natural killer cells and T. lymphocytes to cytolysis. J Exp Med 1986; 164: 814–23.CrossRefGoogle Scholar
  5. 5.
    Mazumder A, Rosenberg SA. Successful immunotherapy of naturel killer-resistant established pulmonary melanome metastases by the intravenous adoptive transfer of syngeneic lymphocytes activated in vitro by Interleukin 2. J Exp Med 1984; 159: 495–507.PubMedCrossRefGoogle Scholar
  6. 6.
    Mule JJ, Shu S, Schwarz SL, Rosenberg SA. Adoptive immunotherapy of established pulmonary metastases with LAK-cells and recombinant Interleukin-2. Science 1984; 225: 1487–9.PubMedCrossRefGoogle Scholar
  7. 7.
    Lafreniere R, Rosenberg SA. Successful immunotherapy of murine experimental hepatic metastases with lymphokine-activated killer cells and recombinant Interleukin-2. Cancer Res 1985;45:3735–41.PubMedGoogle Scholar
  8. 8.
    Rosenberg SA, Lotze MT, Muul LM, et al. Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant INterleukin-2 to patients with metastatic cancer. N Engl J Med 1985; 313: 1485–92.PubMedCrossRefGoogle Scholar
  9. 9.
    Rosenberg SA. Immunotherapy of cancer by systemic administration of lymphoïd cells plus Interleukin-2. J Biol Response Modif 1984; 3: 501–11.Google Scholar
  10. 10.
    Rosenberg SA, Lotze MT, Muul LM, et al. 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; 316: 889–905.PubMedCrossRefGoogle Scholar
  11. 11.
    Muul LM, Director EP, Hyatt C, Rosenberg SA. Large-scale production of hyman lymphokine-activated killer cells for use in adoptive immunotherapy. J Immunol Methods 1986; 88: 265–72.PubMedCrossRefGoogle Scholar
  12. 12.
    Muul LM, Nason-Burchenal K, Carter CS, et al. Development of an automated closed system for generation of human lymphokine-activated killer (LAK) cells for use in adoptive immnotherapy. J Immunol Methods 1987; 101: 171–81.PubMedCrossRefGoogle Scholar
  13. 13.
    Favrot MC, Coze C, Combaret V, et al. Lymphokine-activated killer cell expansion of the culture technique. Mol Biother 1990; 2: 32–37PubMedGoogle Scholar
  14. 14.
    Yanelli JR, Thurman GB, Dickerson SG, et al. An improved method for the generation of human lymphokine activated killer cells. J Immunol Methods 1987; 100: 137–45.CrossRefGoogle Scholar
  15. 15.
    Jadus MR, Thurman GB, Mrowea-Bastin A, Yannelli JR. The generation of human lymphokine activated-killer cells in various serum free-media. J Immunol Methods 1988; 109: 169–74.PubMedCrossRefGoogle Scholar
  16. 16.
    Muul LM, Nason-Burchenal K, Hyatt C, Schwarz J, Slavin S, Director EP, Rosenberg SA. Studies of serum-free culture medium in the generation of kymphokine-activated killer cells. J Immunol Methods 1987; 105: 183–92.PubMedCrossRefGoogle Scholar
  17. 17.
    Whiteside TL, Wang YL, Selker RG, Herberman RB. In vitro generation and antitumor activity of adherant lymphokine-activated killer cells froml the blood of patients with brain tumors. Cancer Res 1988; 48: 6069, 6075.PubMedGoogle Scholar
  18. 18.
    Melder RJ, Whiteside TL, Vujancovic NL, et al. Human adherant lymphokine-activated killer cells (A-LAK). A new approach to generating anti-tumor effects for adoptive immunotherapy. Cancer Res 1988; 48: 3461–68.PubMedGoogle Scholar
  19. 19.
    Hercend T, Farace F, Baume D, et al. Immunotherapy with lymphokine-activated natural killer cells and recombinant Interleukin-2: A feasability trial in metastatic renal cell carcinoma. J Biol Response Modif 1990; 9: 546–55.Google Scholar
  20. 20.
    Ettinghausen SE, Lipford EH, Mule JJ, et al. Recombinant Interleukin-2 stimulates invivo proliferation of adoptively transfered lymphokine-activated killer (LAK) cells. J Immunol 1985; 135: 3623–35.PubMedGoogle Scholar
  21. 21.
    Yang JC, Rosenberg SA. Adoptive cellular therapy: preclinical studies in biological therapy of cancer. In De Vita, Hellman, Rosenberg (eds.)• JB Lippincott Company, 1991: 197–213.Google Scholar
  22. 22.
    Lotze MT, Matory YL, Ettinghausen SE, et al. In vivo administration of purified human Interleukin-2. Half life and immunologic effects and expansion of peripheral lymphoid cells in vivo with recombinant IL-2. J Immunol 1985; 135: 2865–74.PubMedGoogle Scholar
  23. 23.
    Gemlo BT, Palladino MA, Jaffe HS, et al. Circulating cytokines in patients with metastatic cancer treated with recombinant Interleukin-2 and lymphokine-activated killer cells. Cancer Res 1988; 48: 5864–72.PubMedGoogle Scholar
  24. 24.
    Blay JY, Favrot MC, Negrier S, et al. Correlation between clinical response to Interleukin-2 therapy and substained production of tumor necrosis factor. Cancer Res 1990; 50: 2371–4.PubMedGoogle Scholar
  25. 25.
    Yanelli JR, Stevenson GW, Stevenson HC. Cancer adoptive cellular immunotherapy. In: Principles of cancer biotherapy. Eds. Oldham Dekker, Inc. N.Y, 1991: 503–23.Google Scholar
  26. 26.
    Rosenberg SA, Packard BS, Aebersold PM, et al. Use of tumor infiltrating lymphocytes and Interleukin-2 in the immunotherapy of patients with metastatic melanoma, special report. N Engl J Med 1988; 319: 1976–80.CrossRefGoogle Scholar
  27. 27.
    Moertel CG. On lymphokines, cytokines and breakthroughs. J Am Med Assoc 1986; 256: 3141–8.CrossRefGoogle Scholar
  28. 28.
    West WH, Tauer KW, Yanneli JR, et al. Constant infusion recombinant interleukin-2 in adoptive immunotherapy of advanced cancer. N Engl J Med 1987; 316 (15): 898–905.PubMedCrossRefGoogle Scholar
  29. 29.
    Philip T, Negrier S, Mercatello A, et al. Interleukin-2 in the treatment of metastatic renal cell cancer: 77 patients treated in Lyon. In Gardiner (ed). Insights into Immunotherapy. London: Caldwell, 1990: 23–30.Google Scholar
  30. 30.
    Negrier S, Michon J, Floret D, et al. Interleukin-2 and lymphokine-activated killer cells in 15 children with advanced metastatic neuroblastoma. J Clin Oncol 1991; 9: 1363–70.PubMedGoogle Scholar
  31. 31.
    Schoof DD, Gramolini BA, Davidson DL, et al. Adoptive immunotherapy of humain cancer using low-dose recombinant interleukin-2 and lymphokine-activated killer cells. Cancer Res 1988; 48: 5007–10.PubMedGoogle Scholar
  32. 32.
    Dutcher JP, Creekmore S, Weiss GR, et al. A phase II study of interleukin-2 and lymphokine-activated killer cells in patients with metastatic malignant melanoma. J Clin Oncol 1989; 7: 477–85.PubMedGoogle Scholar
  33. 33.
    Thompson JA, Lee DJ, Lindgren CG, et al. Influence of schedule of interleukin-2 administration on therapy with interleukin-2 and lymphokine-activated killer cells. Cancer Res 1989; 49: 235–40.PubMedGoogle Scholar
  34. 34.
    Paciucci PA, Holland JF, Glidewell, et al. Recombinant interleukin-2 continuous infusion and adoptive transfer of recombinant interleukin-2 activated cells in patients with advanced cancer. J Clin Oncol 1989; 7: 869–78.PubMedGoogle Scholar
  35. 35.
    Negrier S, Philip T, Stoter G, et al. Interleukin-2 with or without LAK cells in metastatic renal cell carcinoma: a report of a european multicentre study. Eur J Cancer Clin Oncol 1989; 25: S21–S28.PubMedGoogle Scholar
  36. 36.
    Stahel RA, Sculier J, Jost LM, et al. Tolerance and effectiveness of recombinant interleukin-2 (r-met Hu IL2 (ala 125)) and lymphokine-activated killer cells in patients with metastatic solid tumours. Eur J Cancer Clin Oncol 1989; 25: 965–72.PubMedCrossRefGoogle Scholar
  37. 37.
    Hawkins MJ. PPO Updates IL-2/LAK. Princ Oncol 1989; 3: 1–14.Google Scholar
  38. 38.
    Parkinson DR, Fischer RI, Rayner AA, et al. Therapy of renal cell carcinoma with interleukin-2 and lymphokine-activated killer cells: phase II experience with a hybrid bolus and continuous infusion interleukin-2 regimen. J Clin Oncol 1990; 8: 1630–6.PubMedGoogle Scholar
  39. 39.
    Bar MH, Sznol M, Atkins MB, et al. Metastatic malignant melanoma treated with combined bolus and continuous infusion interleukin-2 and lymphokine-activated killer cells. J Clin Oncol 1990; 8: 1138–47.PubMedGoogle Scholar
  40. 40.
    Dutcher JP, Gaynor ER, Boldt DH, et al. A phase II study of high dose continuous infusion interleukin-2 with lymphokines-activated killer cells: not the optimal schedule for metastatic melanoma. J Clin Oncol 1991; 9: 641–8.PubMedGoogle Scholar
  41. 41.
    Dillman RO, Oldham RK, Tauer KW, et al. Continuous interleukin-2 and lymphokine-activated killer cells for advanced cancer: a national biotherapy study group trial. J Clin Oncol 1991; 9: 1233–40.PubMedGoogle Scholar
  42. 42.
    Margolin KM, Aronson FR, Sznol M, et al. Phase II trial of high dose interleukin-2 and lymphokine-activated killer cells in Hodgkin’s disease and non Hodgkin’s lymphoma J Immunother 1991; 10: 214–20.PubMedCrossRefGoogle Scholar
  43. 43.
    Jacobs SK, Wilson DJ, Kornblith PL, et al. Interleukin-2 or autologous lymphokine-activated killer cell treatment of malignant glioma: phase I trial. Cancer Res 1986: 46: 2101–4.PubMedGoogle Scholar
  44. 44.
    Yoshida S, Tanaka R, Takai N, et al. Local administration of autologous lymphokine-activated killer cell and recombinant interleukin-2 to patients with malignant brain tumors. Cancer Res 1988; 48: 5011–6.PubMedGoogle Scholar
  45. 45.
    Ingram M, Jacques S, Freshwater DB, et al. Salvage immunotherapy of malignant glioma. Arch Surg 1987; 122: 1483–6.PubMedCrossRefGoogle Scholar
  46. 46.
    Merchant RE, Merchant LH, Cook SHS, et al. Intralesional infusion of lymphokineactivated killer (LAK) cells and recombinant interleukin-2 (rIL2) for the treatment of patients withmalignant brain tumor. Neurosurgery 1988; 23: 725–32.PubMedCrossRefGoogle Scholar
  47. 47.
    Barba D, Saris SC, Holder C, et al. Immunotherapy of humain glial tumors: report of multiples dose intratumoral infusions of lymphokine-activated killer cells and interleukin-2. J Neurosurg 1988; 70: 175–82.Google Scholar
  48. 48.
    Himizu K, Okamoto Y, Miyato Y, et al. Adoptive immunotherapy of humain meningeal gliomatosis and carcinomatosis with LAK cells and recombinant interleukin-2. J Neurosurg 1987;66:519–21.CrossRefGoogle Scholar
  49. 49.
    Lotze MT, Custer MC, Rosenberg SA Intraperitoneal administration of interleukin-2 in patients with cancer. Arch Surg 1986; 121: 1373.PubMedCrossRefGoogle Scholar
  50. 50.
    Urba WJ, Clark JW, Steis RG, et al. Intraperitoneal lymphokine-activated killer cell/interleukin-2 therapy in patients with intra-abdominal cancer: immunologic considerations. J Nat Cancer Inst 1989; 81: 602–11.PubMedCrossRefGoogle Scholar
  51. 51.
    Yashumoto K, Miyazaki K, Nagashima A, et al. Induction of lymphokine-activated killer cells by intrapleural instillations of recombinant interleukin-2 in patients with malignant pleurisy due to lung cancer. Cancer Res. 1987; 47: 2184–7.Google Scholar
  52. 52.
    Pizza G, Severini G, Menniti C, et al. Intralymphatic administration of interleukin-2 in cancer patients. A pilot study. Lymphokine Res 1988; 7: 45–54.PubMedGoogle Scholar
  53. 53.
    Abbruzzese JL, Levin B. Treatment of advanced colorectal cancer. Hem Oncol Clin N Am 1989; 3: 135–53.Google Scholar
  54. 54.
    Hamblin JJ, Davies B, Sadullah S, et al. A phase II study of the treatment of metastatic malignant melanoma with a combination of Dacarbazine, Cis-platin, Inteleukin-2 (IL2) and alfa-Interferon (IFN) in Proceed ASCO. J Clin Oncol 1991; 10: 294 (abs).Google Scholar
  55. 55.
    Demchak PA, Mier JW, Robert NJ, et al. Interleukin-2 and high dose Cisplatin in patients with metastatic melanoma: a pilot study. J Clin Oncol 1991; 9: 1821–30.PubMedGoogle Scholar
  56. 56.
    Rosenberg SA. The development of new immunotherapies for the treatment of cancer using Interleukin-2. Ann Surg 1988; 208: 121–35.PubMedCrossRefGoogle Scholar
  57. 57.
    Atzpodien J, Korfer A, Franks CR, Poliwoda M, Kirchner H. Home therapy with recombinant interleukin-2 and interferon 2 in advanced malignancies. Lancet 1990; 335: 1509–12.PubMedCrossRefGoogle Scholar
  58. 58.
    Rosenberg SA, Aebersold P, Cornetta K, et al. Gene transfer into humans: immunotherapy of patients with advanced melanoma using tumor infiltrating lymphocytes modified by retroviral gene transduction. N Engl J Med 1990; 323: 570–8.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 1993

Authors and Affiliations

  • Sylvie Negrier
  • Thierry O. Philip

There are no affiliations available

Personalised recommendations