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Autologous Antileukemia Cytotoxicity Induced by PBL and BM Culture with rIL-2: Use in Autologous BMT for Inducing GVL?

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Cytokines in Hemopoiesis, Oncology, and AIDS

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Abstract

Increasing evidence indicates that natural killer (NK) cells may play a role in defense against leukemia [1, 2]: low NK responding individuals have an increased susceptibility to leukemia; patients with acute leukemia (AL), even in complete remission (CR), have a defect in NK cell function [3,4]; and NK clones with antileukemia activity have been observed following Bone Marrow transplantation (BMT) [5]. Allo-BMT is more effective than auto-BMT [6, 7] with regard not only to the transplantation of “clean” BM but principally to the immunologic stimulation induced by the graft-versus-host (GVH) response [8]. The question is:Would it be possible to induce such an antileukemia effect when using rIL-2 in auto-BMT? LAK cells obtained after 3–5 days culture of PBL with IL-2 are cytotoxic against NK-resistant cell lines without major histocompatibility complex (MHC) restriction [9]. Progenitors and effectors have the LGL morphology. The effectors are principally (95%) NK-activated cells (CD3−, TCR−, CD16+, NKH1+) and only 5% are “NK-like” T cells (CD3+, TCRγδ+, NKH1+) [10–13]. Several reports mention the susceptibility of leukemic blast cells to lysis by LAK cells and IL-2 [14–22] but to date there are still few reports concerned with autologous antileukemia cytotoxicity in leukemic patients in CR.

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References

  1. Lotzova E, Savary CA, Herberman RB, Dicke KA (1986) Can NK cells play a role in therapy of leukemia? Nat Immun Cell Growth Regul 5:61–63

    PubMed  CAS  Google Scholar 

  2. Talpaz M, Bielski M, Hersh EM (1982) Studies of natural killer cell activity and ADCC cytotoxicity among patients with acute leukemia in complete remission. Cancer Immunol Immunother 14:98–98

    Article  Google Scholar 

  3. Jermy A, Lilleyman JS, Jennings R, Rees RC (1987) Spontaneous natural killer cell activity in childhood acute lymphoblastic leukaemia. Eur J Cancer Clin Oncol 23 (9):1365–1370

    Article  PubMed  CAS  Google Scholar 

  4. Mageed AA, Findley HW, Franco C, Shinghapakdi S, Alvarado C, Chan WC, Ragab A H (1987) Natural killer cells in children with acute leukemia. The effect of IL2. Cancer 60:2913–2918

    Article  PubMed  CAS  Google Scholar 

  5. Hercend T, Takvorian T, Nowill A, Tantravahi R, Moingeon P, Anderson KC, Murray C, Bohuon C, Ythier A, Ritz J (1986) Characterization of NK cells with antileukemia activity following allogeneic bone marrow transplantation. Blood 67 (3):722–728

    PubMed  CAS  Google Scholar 

  6. Sanders JE, Thomas ED, Buckner CD, Doney K (1987) Marrow transplantation for children with ALL in 2nd remission. Blood 70 (l):324–326

    PubMed  CAS  Google Scholar 

  7. Souillet G, Leverger G, Bordigoni P, Lamagnere JP, Lemerle S, Reiffers J, Plouvier E, Boilletot A, Rubie H, Demeocq F, Lutz P, Herve P, Schaison G (1989) Disappointing results of autologous BMT for ALL in 2nd remission for relapse “on therapy”. A French cooperative study (FAG and RALL protocols) European Cooperative Group for Bone Marrow Transplantation, Badgastein (abstr no 302 )

    Google Scholar 

  8. Weiden PL, Flournoy M, Thomas ED (1979) Antileukemic effects of GVH disease in human recipients of allogeneic marrow grafts. N Engl J Med 300:1068–1073

    Article  PubMed  CAS  Google Scholar 

  9. Grimm EA, Mazumder A, Zhang HZ, Rosenberg SA (1982) Lymphokine activated killer cell phenomenon:lysis of NK resistant fresh solid tumor cells by IL2 activated autologous human peripheral blood lymphocyte. J Exp Med 155:1823–1841

    Article  PubMed  CAS  Google Scholar 

  10. Phillips JH, Lanier LL (1986) Dissection of the lymphokine activated killer phenomenon. J Exp Med 164:814–825

    Article  PubMed  CAS  Google Scholar 

  11. Herberman RB (1987) LAK cell activity:characteristics of effector cells and their progenitors in blood and spleen. Immunol Today 8 (6):178–181

    Article  Google Scholar 

  12. Reynolds CW, Ortaldo JR (1987) Natural killer activity:the definition of a function rather than a cell type. Immunol Today 8 (6):172–174

    Article  Google Scholar 

  13. Lotzova E, Herberman RB (1987) Reassessment of LAK phenomenology:a review. Nat Immun Cell Growth Regul 6:109–115

    PubMed  CAS  Google Scholar 

  14. Dawson MM, Johnston D, Taylor GM, Moore M (1986) Lymphokine activated killing of fresh human leukemias. Leuk Res 10 (6):683–688

    Article  PubMed  CAS  Google Scholar 

  15. Thompson JA, Peace DJ, Klarnet JP, Kern DE, Greenberg PD, Cheever MA (1986) Eradication of disseminated murine leukemia by treatment with high dose IL2. J Immunol 137 (11):3675–3680

    PubMed  CAS  Google Scholar 

  16. Oshimi K, Oshimi Y, Akutsu M, Takei Y, Saito H, Okada M, Mizoguchi H (1986) Cytotoxicity of IL2 activated lymphocytes for leukemia and lymphoma cells. Blood 68:938–948

    PubMed  CAS  Google Scholar 

  17. Lotzova E, Savary CA, Herberman RB (1987) Induction of NK cell activity against fresh human leukemia in culture with IL2. J Immunol 138 (8):2718–2727

    PubMed  CAS  Google Scholar 

  18. Lotzova E, Savary CA, Herberman RB (1987). Inhibition of clonogenic growth of fresh leukemia cells by unstimulated and IL2 stimulated NK cells of normal donors. Leuk Res (12):1059–1066

    Article  Google Scholar 

  19. Bernaudin F, Beaujean F, Lemerle S, Kuentz M, Cordonnier C, Vernant JP, Reinert P, Duedari N, Bernaudin JF, (1988) Induction of antileukemia cytotoxicity by culture with R-IL2. Bone Marrow Transplant 3 [Suppl 1]

    Google Scholar 

  20. Bernaudin F, Beaujean F, Kuentz M, Lemerle S, Lelong F, Reinert P, Cordonnier C, Vernant JP, Bernaudin JF (1988) Cytotoxicity against autologous lymphoblasts by R-IL2 activated killer (LAK) cells obtained from patients with ALL. Blood 72 [Suppl 1] (5):189a

    Google Scholar 

  21. Adler A, Chervenick PA, Whiteside TL, Lotzova E, Herberman RB (1988) IL2 induction of LAK activity in the peripheral blood and bone marrow of acute leukemia patients. I. Feasibility of LAK generation in adult patients with active disease and in remission. Blood 71 (3):709–716

    PubMed  CAS  Google Scholar 

  22. Findley HW, Mageed AA, NASR SA, RAGAB AH (1988) Recombinant IL2 activates peripheral blood lymphocytes from children with acute leukemia to kill autologous leukemic cells. Cancer 62:1928–1931

    Article  PubMed  Google Scholar 

  23. Koo GC, Manyak CL (1986) Generation of cytotoxic cells from murine bone marrow by human R-IL2. J Immunol 137 (6):1751–1756

    PubMed  CAS  Google Scholar 

  24. Lotzova E, Savary CA (1987) Generation of NK cell activity from human bone marrow. J Immunol 139 (l):279–284

    PubMed  CAS  Google Scholar 

  25. Pollack SB, Rosse C (1987) The primary role of murine bone marrow in the production of natural killer cells:a cytokinetic study. J Immunol 139 (7):2149–2156

    PubMed  CAS  Google Scholar 

  26. Migliorati G. Cannarile L, Herberman RB, Bartocci A, Stanley ER, Riccardi C (1987) Role of IL2 and H-l in the generation of mouse NK cells from primitive bone marrow precursors. J Immunol 138 (11):3618–3625

    PubMed  CAS  Google Scholar 

  27. Barlozzari T, Herberman RB, Reynolds CW (1987) Inhibition of pluri potent hematopoietic stem cells of bone marrow by large granular lymphocytes. Proc Natl Acad Sci USA 84:7691–7695

    Article  PubMed  CAS  Google Scholar 

  28. Takahashi M, Oshimi K, Saito H, Mizoguchi H (1988) Inhibition of human granulocyte macrophage colony formation by IL2 treated lymphocytes. Exp Hematol 16:226–230

    PubMed  CAS  Google Scholar 

  29. Ettinghausen SE, Moore JG, White DE, Platanias L, Young NS, Rosenberg SA (1987) Hematologic effects of immunotherapy with LAK cells and R-IL2 in cancer patients. Blood 69 (6):1654–1660

    PubMed  CAS  Google Scholar 

  30. Piguet PF, Grau G, Irle C, Vassalli P (1986) Administration of R-IL2 to mice enhances production of hemopoietic and NK cells. Eur J Immunol 16:1257–1261

    Article  PubMed  CAS  Google Scholar 

  31. Matera L, Santoli D, Garbarino G, Pegoraro L, Bellone G, Pagliardi G (1986) Modulation of in vitro myelopoiesis by LGL:different effects on early and late progenitor cells. J Immunol 136 (4):1260–1265.

    PubMed  CAS  Google Scholar 

  32. Voogt PJ, Falkenburg JH F, Fibbe WE, Veenhof WFJ, Hamilton M, Van Krimpen BA, Bolhuis RLH (1989) Normal hematopoietic progenitor cells and malignant lymphohematopoietic cells show different susceptibility to direct cell mediated MHC non restricted lysis by T cell receptors-/CD3-, T cell receptor +/CD3+ and T cell receptor B+/CD3+ lymphocytes. J Immunol 142 (5):1774–1780

    PubMed  CAS  Google Scholar 

  33. Nagler A, Greenberg PL, Lanier LL, Philips JH, (1988) The effects of R-IL2 activated natural killer cells on autologous peripheral blood hematopoietic progenitors. J Exp Med 168:47–54

    Article  PubMed  CAS  Google Scholar 

  34. Spooncer E, Dexter TM (1983) Transplantation of long term cultured bone marrow cells. Transplantation 35 (6):624–626

    Article  PubMed  CAS  Google Scholar 

  35. Long GS, Hiserodt JC, Harnaha JB, Cramer DV (1988) Lymphokine activated killer cell purging of leukemia cells from bone marrow prior to syngeneic transplantation. Transplantation 46 (3):433–438

    Article  PubMed  CAS  Google Scholar 

  36. Beaujean F, Bernaudin F, Kuentz M, Lemerle S, Vernant JP, Duedari N (1989) Evaluation of LAK cell induction and CFU-GM recovery in long term bone marrow culture with R-IL2. European Cooperative Group for Bone Marrow Transplantation Badgastein (abstr)

    Google Scholar 

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Authors
  1. F. Bernaudin
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  2. F. Beaujean
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  3. M. Kuentz
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  4. S. Lemerle
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  5. F. Lelong
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  6. P. Reinert
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  7. J. P. Vernant
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  8. J. F. Bernaudin
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Editor information

Editors and Affiliations

  1. Abt. Hämatologie und Onkologie, Medizinische Hochschule Hannover, Konstanty-Gutschow-Straße 8, D-3000, Hannover 61, Germany

    Mathias Freund  & Hartmut Link  & 

  2. Abt. Pädiatrische Hämatologie und Onkologie, Medizinische Hochschule Hannover, Konstanty-Gutschow-Straße 8, D-3000, Hannover 61, Germany

    Karl Welte

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© 1990 Springer-Verlag, Berlin Heidelberg

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Bernaudin, F. et al. (1990). Autologous Antileukemia Cytotoxicity Induced by PBL and BM Culture with rIL-2: Use in Autologous BMT for Inducing GVL?. In: Freund, M., Link, H., Welte, K. (eds) Cytokines in Hemopoiesis, Oncology, and AIDS. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-75510-1_35

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  • DOI: https://doi.org/10.1007/978-3-642-75510-1_35

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-52281-2

  • Online ISBN: 978-3-642-75510-1

  • eBook Packages: Springer Book Archive

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