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Human Lymphokine-Activated Killer Cells and Their Potential for Cancer Therapy

  • E. A. Grimm

Abstract

Data from numerous animal tumor models have led to the consensus that the cellular immune system contains the capacity to regulate autologous tumor growth. Differences exist with respect to the observed effector system(s) responsible for tumor regression: monocytes, helper T cells, killer T cells of varying and distinct phenotypes, cell populations expressing natural killer (NK) activity, and lymphokine-activated killer (LAK) cells each have been reported to be operative in the regulation of cancer. The recent development of DNA-produced immunological “hormones,” often called “cytokines,” has provided an unequaled opportunity to study basic aspects of immune regulation. In the USA, as well as in several other countries, the public has become increasingly aware of and interested in the potential therapeutic application of these cytokines, and hence they are already in the initial stages of testing for their value in cancer therapy.

Keywords

Adoptive Therapy Autologous Lymphocyte Peripheral Blood Lympho Autochthonous Tumor Stromal Cell Sarcoma 
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.

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References

  1. 1.
    Grimm EA, Mazumder A, Rosenberg SA (1982) In vitro growth of cytotoxic human lymphocytes. V. Generation of allospeciflc cytotoxic lymphocytes to nonimmunogenie antigen by supplementation of in vitro sensitization with partially purified T cell growth factor ( PP-TCGF ). Cell Immunol 70: 248–259Google Scholar
  2. 2.
    Grimm EA, Mazumder A, Zhang HZ, Rosenberg SA (1982) The lymphokine activated killer cell phenomenon: lysis of NK resistant fresh solid tumor cells by IL–2 activated autologous human peripheral blood lymphocytes. J Exp Med 155: 1823–1841PubMedCrossRefGoogle Scholar
  3. 3.
    Grimm EA, Rosenberg SA (1984) The human lymphokine-activated killer cell phenomenon. In: Pick E (ed) The lymphokines. Academic, New York, pp 279–311Google Scholar
  4. 4.
    Grimm EA (1986) Lymphokine activated killing. BBA Rev Cancer 865 (3): 267–279Google Scholar
  5. 5.
    Grimm EA, Robb RJ, Roth JA, Neckers LM, Lachman L, Wilson DJ, Rosenberg SA (1983) The lymphokine activated killer cell phenomenon. III. Evidence that IL–2 alone is sufficient for direct activation of PBL into LAK. J Exp Med 158: 1356–1361PubMedCrossRefGoogle Scholar
  6. 6.
    Lotze MT, Matory YL, Ettinghausen SE, Rayner AA, Sharrow SO, Seipp CA, 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: 2865–2875PubMedGoogle Scholar
  7. 7.
    Bradley EC, Doyle M, deGroat S, Damle NK, Doyle LV, Rudolph AR, Issell BF (1987) LAK induction in vivo in patients treated with interleukin–2 may be necessary for tumor regression. Proc Am Assoc Cancer Res 28: 407Google Scholar
  8. 8.
    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 Rosenberg SA, Lotze MT, Muul LM(1985) Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin–2 to patients with metastatic cancer. New Engl J Med 313: 1485–1492Google Scholar
  9. 9.
    West WH, Taur KW, Yannelli JR(1987) Constant-infusion recombinant interleukin–2 in adoptive immunotherapy of advanced cancer. New Engl J Med 316: 898–905PubMedCrossRefGoogle Scholar
  10. 10.
    Jacobs SK, Wilson DJ, Kornblith PL, Grimm EA (1986) Interleukin–2 and autologous lymphokine activated killer (LAK) cells in the treatment of malignant glioma: preliminary report. J Neurosurg 64: 743–749PubMedCrossRefGoogle Scholar
  11. 11.
    Jacobs SK, Wilson DJ, Kornblith PL, Grimm EA (1986) Interleukin–2 or autologous lymphokine activated killer cell treatment of malignant glioma: phase I trial. Cancer Res 46: 2101PubMedGoogle Scholar
  12. 12.
    Jacobs SK, Kornblith PL, Wilson DJ, Grimm EA (1986) In vitro killing of human glioblastoma by interleukin–2 activated autologous lymphocytes. J Neurosurg 64: 114–117PubMedCrossRefGoogle Scholar
  13. 13.
    Adler A, Stein JA, Kedar E, Naor D, Weiss DW (1984) Intralesional injection of interleu-kin-2-expanded autologous lymphocytes in melanoma and breast cancer patients: a pilot study. J Biol Response Mod 3: 491–500PubMedGoogle Scholar
  14. 14.
    Pizza G, Severini G, Menniti D, De Vinci C, Corrado F (1984) Tumor regression after intralesional injection of interleukin–2 (IL–2) in bladder cancer. Preliminary report. Int J Cancer 34: 359–369Google Scholar
  15. 15.
    Grimm E A, Ammann RA, Crump W, Durett A, Hester JP, Lagoo-Deenadalayan S, Owen-Schaub LB (1988) TGF-beta inhibits the in vitro induction of lymphokine-activated killing activity. Cancer Immunol Immunother 27: 53–55PubMedCrossRefGoogle Scholar
  16. 16.
    Grimm E A, Owen-Schaub LB, Loudon WG, Yagita M (1988) Lymphokine-activated killer cells: induction and function. Ann NY Acad Sci 532: 480–481CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1989

Authors and Affiliations

  • E. A. Grimm

There are no affiliations available

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