Susceptibility of Human Leukemia Cells to Allogeneic and Autologous Lymphokine-Activated Killer Cells and Its Augmentation by Exposure of Leukemia Target Cells to Cytotoxic Drugs In Vitro and In Vivo

  • J. V. Teichmann
  • W.-D. Ludwig
  • E. Thiel
Conference paper
Part of the Recent Results in Cancer Research book series (RECENTCANCER, volume 131)

Abstract

Interleukin-2- (IL-2-)activated cytotoxic effector cells, known as lymphokine- activated killer (LAK) cells, lyse a wide variety of fresh solid tumor cells (Grimm et al. 1982; Itoh et al. 1986) as well as fresh noncultured leukemia cells (Oshimi et al. 1986; Lotzova et al. 1987; Fierro et al. 1988; Teichmann et al. 1989) in a fashion not restricted by the major histocompatibility complex (MHC). LAK cell cytotoxicity is predominantly mediated by CD3-/CD56+ activated natural killer (NK) cells and only to a small degree by MHC-unrestricted CD3+/CD56+ T cells (Phillips and Lanier 1986; Herberman et al. 1987; Tilden et al. 1987; Saito et al. 1988). Human leukemia cells possess a distinct LAK cell susceptibility which varies considerably in different subtypes of leukemia (Teichmann et al. 1992). Maximal cytolysis by activated effector cells is desirable for therapy. The current study therefore aimed at investigating whether in vitro exposure of leukemic cells to cytotoxic agents, relevant for leukemia treatment, can augment the susceptibility of fresh noncultured leukemia cells to LAK cell lysis. In addition, we also studied the susceptibility of leukemia cells both before and after exposure to cytotoxic drugs given in vivo during induction chemotherapy.

Keywords

Toxicity Chromium Lymphoma Leukemia Oncol 

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References

  1. Ades EW, McKemie III CR, Wright S, Peacocke N, Pantazis C, Lockhart III WL (1987) Chemotherapy subsequent to recombinant interleukin-2 immunotherapy: protocol for enhanced tumoricidal activity. Nat Immun Cell Growth Regul 6:260–268PubMedGoogle Scholar
  2. Agah R, Malloy B, Kerner M, Mazumder A (1989) Generation and characterization of IL-2-activated bone marrow cells as a potent graft vs tumor effector in transplantation. J Immunol 143: 3093–3099PubMedGoogle Scholar
  3. Allavena P, Damia G, Colombo T, Maggioni D, D’lncalci M, Mantovani A (1989) Lymphokine-activated killer ( LAK) and monocyte-mediated cytotoxicity on tumor cell lines resistant to antitumor agents. Cell Immunol 120: 250–258PubMedCrossRefGoogle Scholar
  4. Billaud M, Calender A, Seigneurin JM, Lenoir GM (1987) LFA-1, LFA-3, and ICAM-1 expression in Burkitt’s lymphoma. Lancet 11: 1327–1328CrossRefGoogle Scholar
  5. Boyed AW, Wawryk SO, Burns GF, Fecondo JV (1988) Intercellular adhesion molecule-1 (ICAM-1) has a central role in cell-cell contact mediated immune mechanisms. Proc Natl Acad Sci USA 85: 3095–3099CrossRefGoogle Scholar
  6. Boyed AW, Dunn SM, Fecondo JV, Culvenor JG, Duehrsen U, Burns GF, Wawryk SO (1989) Regulation of expression of a human intercellular adhesion molecule (ICAM-1) during lymphohematopoietic differentiation. Blood 73: 1896–1903Google Scholar
  7. Buechner T, Hiddemann W, Maschmeyer G, Ludwig WD, Loeffler H, Nowrousian M, Aul C, Heinecke A (1990) How to improve therapy for adult acute myeloid leukemia: studies of the AML Cooperative Group in the Federal Republic of Germany. J Cancer Res Clin Oncol 116: 97–99CrossRefGoogle Scholar
  8. Colotta F, Peri G, Villa A, Mantovani A (1984) Rapid killing of actinomycin D-treated tumor cells by human mononuclear cells. J Immunol 132: 936–944PubMedGoogle Scholar
  9. Djeu JY, Blanchard DK (1988) Lysis of human monocytes by lymphokine-activated killer cells. Cell Immunol 111: 55–65PubMedCrossRefGoogle Scholar
  10. Dutcher JP, Creekmore S, Weiss GR, Margolin K, Markowitz AB, Roper M, Parkinson D, Ciobanu N, Fisher RI, Boldt DH, Doroshow JH, Rayner AA, Hawkins M, Atkins M (1989) A phase II study of interleukin-2 and lymphokine- activated killer cells in patients with metastatic malignant melanoma. J Clin Oncol 7: 477–485PubMedGoogle Scholar
  11. Fierro MT, Liao XS, Lusso P, Bonferroni M, Matera L, Cesano A, Lista P, Arione R, Forni G, Foa R (1988) In vitro and in vivo susceptibility of human leukemic cells to lymphokine activated killer activity. Leukemia 2: 50–54PubMedGoogle Scholar
  12. Fisher RI, Coltman CA, Doroshow JH, Rayner AA, Hawkins MJ, Mier JW, Wiernik P, McMannis JD, Weiss GR, Margolin KA, Gemlo BT, Hoth DF, Parkinson DR, Paietta E (1988) Metastatic renal cancer treated with interleukin-2 and lymphokine-activated killer cells. Ann Intern Med 108: 518–523PubMedGoogle Scholar
  13. Gambacorti-Passerini C, Radrizzani M, Marolda R, Belli F, Sciorelli G, Galazka AR, Schindler JD, Cascinelli N, Parmiani G (1988) In vivo activation of lymphocytes in melanoma patients receiving escalating doses of recombinant interleukin- 2. Int J Cancer 41: 700–706PubMedCrossRefGoogle Scholar
  14. Grimm EA, Mazumder A, Zhang HZ, Rosenberg SA (1982) Lymphokine-activated killer cell phenomenon. Lysis of natural killer-resistant fresh solid tumor cells by interleukin 2-activated autologous human peripheral blood lymphocytes. J Exp Med 155: 1823–1841PubMedCrossRefGoogle Scholar
  15. Herberman RB, Hiserodt JC, Vujanovic N, Balch CM, Lotzova E, Bolhuis R, Golub S, Lanier LL, Phillips JH, Riccardi C, Ritz J, Santoni A, Schmidt RE, Uchida A (1987) Lymphokine-activated killer cell activity. Characteristics of effector cells and their progenitors in blood and spleen. Immunol Today 8: 178–181CrossRefGoogle Scholar
  16. Itoh K, Tilden AB, Balch CM (1986) Lysis of human solid tumor cells by lymphokine- activated natural killer cells. J Immunol 136: 3910–3915PubMedGoogle Scholar
  17. Kunkel LA, Welsh RM (1981) Metabolic inhibitors render “resistant” target cells sensitive to natural killer cell-mediated lysis. Int J Cancer 27: 73–79PubMedCrossRefGoogle Scholar
  18. Leroux JY, Mercier G, Oth D (1986) Enhancement of murine lymphoma cell lysability by CTL and by LAK cells after treatments with mitomycin C and with adriamycin. Int J Immunopharmacol 8: 369–375PubMedCrossRefGoogle Scholar
  19. Lichtenstein A, Pende KD (1986) Enhancement of natural killer cytotoxicity by cis-diammine-dichloroplatinum ( II) in vivo and in vitro. Cancer Res 46: 639–644PubMedGoogle Scholar
  20. Lotzovä E, Savary CA, Herberman RB (1987) Induction of NK cell activity against fresh human leukemia in culture with interleukin 2. J Immunol 138: 2718–2727PubMedGoogle Scholar
  21. Ludwig WD, Bartram CR, Ritter J, Raghavachar A, Hiddemann W, Heil G, Harbott J, Seibt-Jung H, Teichmann JV, Riehm H (1988) Ambiguous phenotypes and genotypes in 16 children with acute leukemia as characterized by multiparameter analysis. Blood 71: 1518–1528PubMedGoogle Scholar
  22. Marlin SD, Springer TA (1987) Purified intercellular adhesion molecule-1 (ICAM-1) is a ligand for lymphocyte function-associated antigen-1 (LFA-1). Cell 51: 813–819PubMedCrossRefGoogle Scholar
  23. Mitchell MS, Kempf RA, Harel W, Shau H, Boswell WD, Lind S, Bradley EC (1988) Effectiveness and tolerability of low-dose cyclophosphamide and low-dose intravenous interleukin-2 in disseminated melanoma. J Clin Oncol 6: 409–424PubMedGoogle Scholar
  24. Nagarkatti M, Nagarkatti PS, Kaplan AM (1988) Differential effects of BCNU on T cell, macrophage, natural killer and lymphokine-activated killer cell activities in mice bearing a syngeneic tumor. Caner Immunol Immunother 27: 38–46Google Scholar
  25. Oshimi K, Oshimi Y, Akutsu M, Takei Y, Saito H, Okada M, Mizoguchi H (1986) Cytotoxicity of interleukin-2-activated lymphocytes for leukemia and lymphoma cells. Blood 68: 938–948PubMedGoogle Scholar
  26. Panayotides P, Porwit A, Sjögren AM, Wasserman J, Reizenstein P (1988) Resistance of some leukemic blasts to lysis by lymphokine activated killer ( LAK) cells. Eur J Haematol 40: 362–367PubMedCrossRefGoogle Scholar
  27. Papa MZ, Yang JC, Vetto JT, Shiloni E, Eisenthal A, Rosenberg SA (1988) Combined effects of chemotherapy and interleukin-2 in the therapy of mice with advanced pulmonary tumors. Cancer Res 48: 122–129PubMedGoogle Scholar
  28. Phillips JH, Lanier LL (1986) Dissection of the lymphokine-activated killer phenomenon. Relative contribution of peripheral blood natural killer cells and T lymphocytes to cytolysis. J Exp Med 164: 814–825PubMedCrossRefGoogle Scholar
  29. 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: 51–63PubMedCrossRefGoogle Scholar
  30. Rayner AA, Grimm EA, Lotze MT, Chu EW, Rosenberg SA (1985) Lymphokine-activated killer (LAK) cells. Analysis of factors relevant to the immunotherapy of human cancer. Cancer 55: 1327–1333PubMedCrossRefGoogle Scholar
  31. Rosenberg SA, Lotze MT, Muul LM, Chang AE, Avis FP, Leitman S, Linehan WM, Robertson CN, Lee RE, Rubin JT, Seipp CA, Simpson C, White DE (1987) 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 316: 889–897PubMedCrossRefGoogle Scholar
  32. Rothlein R, Dustin ML, Marlin SD, Springer TA (1986) A human intercellular adhesion molecule (ICAM-1) distinct from LFA-1. J Immunol 137: 1270–1274PubMedGoogle Scholar
  33. Saito H, Oshimi K, Oshimi Y, Mizoguchi H (1988) Characterization of interleukin 2- expanded human peripheral blood lymphocytes: Not only NKH-1+ NK cells but also NKH-1+ and NKH-1- T cells are LAK effectors. Cell Immunol 117: 253–263PubMedCrossRefGoogle Scholar
  34. Salup RR, Back TC, Wiltrout RH (1987) Successful treatment of advanced murine renal cell cancer by bicompartmental adoptive chemoimmunotherapy. J Immunol 138: 641–647PubMedGoogle Scholar
  35. Sondel PM, Hank JA, Kohler PC, Chen BP, Minkoff DZ, Molenda JA (1986) Destruction of autologous human lymphocytes by interleukin-2-activated cytotoxic cells. J Immunol 137: 502–511PubMedGoogle Scholar
  36. Sosman JA, Kohler PC, Hank J, Moor KH, Bechhofer R, Storer B, Sondel PM (1988) Repetitive weekly cycles of recombinant human interleukin-2: responses of renal carcinoma with acceptable toxicity. J Natl Cancer Inst 80: 60–63PubMedCrossRefGoogle Scholar
  37. Teichmann JV, Ludwig WD, Seibt-Jung H, Thiel E (1989) Induction of lymphokine-activated killer ( LAK) cells against human leukemia cells in vitro. Blut 59: 21–24PubMedCrossRefGoogle Scholar
  38. Teichmann JV, Ludwig W-D, Thiel E (1992) Susceptibility of human leukemia to allogeneic and autologous lymphokine-activated killer cells in an analysis of 252 samples. Nat Immun 11: 117–132PubMedGoogle Scholar
  39. Thiel E, Kranz BR, Raghavachar A, Bartram CR, Löffler H, Messerer D, Ganser A, Ludwig WD, Büchner T, Hoelzer D (1989) Prethymic phenotype and genotype of pre-T (CD 7+/ER-) — cell leukemia and its clinical significance within adult acute lymphoblastic leukemia. Blood 73: 1247–1258PubMedGoogle Scholar
  40. Tilden AB, Itoh K, Balch CM (1987) Human lymphokine-activated killer (LAK) cells: identification of two types of effector cells. J Immunol 138: 1068–1073PubMedGoogle Scholar
  41. Uchida A, Klein E (1985) Natural cytotoxicity of human blood monocytes and natural killer cells and their cytotoxic factors: discriminating effects of actinomycin D. Int J Cancer 35: 691–699PubMedCrossRefGoogle Scholar
  42. van der Harst D, Brand A, van Luxemburg-Heys SAP, Kooy-Winkelaar EMC, van Rood JJ (1989) Lymphokine-activated killer cell functions in patients with leukemic B-lympho-proliferative diseases. Blood 74: 2464–2470PubMedGoogle Scholar
  43. West WH, Tauer KW, Yannelli JR, Marshall GD, Orr DW, Thurman GB, Oldham RK (1987) Constant infusion of recombinant interleukin-2 in adoptive immunotherapy of advanced cancer. N Engl J Med 316: 898–905PubMedCrossRefGoogle Scholar
  44. Ziegler-Heitbrock HWL, Erhardt J, Riethmüller G (1983) Treatment of fresh human leukaemia cells with actinomycin D enhances their lysability by natural killer cells. Br J Cancer 48: 507–514PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin · Heidelberg 1993

Authors and Affiliations

  • J. V. Teichmann
    • 1
  • W.-D. Ludwig
    • 1
  • E. Thiel
    • 1
  1. 1.Department of Hematology and Oncology, Universitätsklinikum SteglitzFree University of BerlinBerlin 45Fed. Rep. of Germany

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