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Use of human leukocyte antigen-mismatched allogeneic lymphokine-activated killer cells and interleukin-2 in the adoptive immunotherapy of patients with malignancies

  • Published:
Biotherapy

Abstract

Clinical effects and side effects were studied in the adoptive immunotherapy of patients bearing malignant diseases using human leukocyte antigen (HLA)-mismatched allogeneic lymphokine-activated killer (LAK) cells. Allogeneic LAK cells were induced from peripheral blood lymphocytes (PBL) of normal donors by means of initial stimulation with pokeweed mitogen (PWM). Six of 15 patients applied in the adoptive immunotherapy showed clinical effects such as partial or complete regression of pulmonary metastasis, pleural effusion and primary tumor. All pulmonary metastatic lesions were eliminated in one case by this adoptive immunotherapy combined with chemotherapy. Generally toxic effects were chillness, fever and general fatigue which were reversible, and no allergic side effects occurred even though allogeneic LAK cells were injected frequently except one patient who showed preshock like symptom accompanied with leukocytopenia and continuous hypotension immediately after infusion but was finally rescued. In the patients who received more than 1011 of allogeneic LAK cells, anti-HLA class I antibodies appeared without any evidence of autoantibody. However, immunological side effects were never experienced after injection of allogeneic LAK cells even when the anti-HLA class I antibodies appeared in the patients. Taken together, allogeneic LAK cells could be considered as alternative therapy for patients with malignancies who could not supply sufficient materials of autologous LAK cells.

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Abbreviations

PWM:

pokeweed mitogen

LAK:

lymphokine-activated killer

IL-2:

interleukin 2

PEL:

peripheral blood lymphocytes

TIL:

tumor-infiltrating lymphocytes

GVHD:

graft-versus-host disease

HLA:

human leukocyte antigen

References

  1. Bukowski RM, Sharfman W, Murthy S. Clinical results and characterization of tumor-infiltrating lymphocytes with or without recombinant interleukin 2 in human metastatic renal cell carcinoma. Cancer Res 1991; 51: 4199–205.

    PubMed  Google Scholar 

  2. Champlin R, and Gale RP. Bone marrow transplantation for acute leukemia: Recent advances and comparison with alternative therapies. Semin Hematol 1987; 24: 55–67.

    PubMed  Google Scholar 

  3. European Group for Bone Marrow Transplantation: Allogeneic bone marrow transplantation for leukemia in Europe. Lancet 1988; 1: 1379–82.

    Google Scholar 

  4. Finke JH, Rayman P, Alexander J, Edinger M, Tubbs, RR, Connelly R, Pontes E and Bukowski R. Characterization of the cytolytic activity of CD4+ and CD8+ tumor-infiltrating lymphocytes in human renal cell carcinoma. Cancer Res 1990; 50: 2363–2370.

    PubMed  Google Scholar 

  5. Itoh K, Platsoucas CD and Balch CM. Autologous tumorspecific cytotoxic T lymphocytes in the infiltrate of human metastatic melanomas: Activation by interleukin 2 and autologous tumor cells and involvement of the T cell receptor. J Exp Med 1988; 168: 1419–41.

    PubMed  Google Scholar 

  6. Kawakami Y, Zakut R, Topalian SL. Shared human melanoma antigens. Recognition by tumor-infiltrating lymphocytes in HLA-A2.1-transfected melanomas. J Immunol 1992; 148: 638–43.

    PubMed  Google Scholar 

  7. Kersey JH, Weisdorf D, Nesbit ME, Lebien TW, Woods WG, Mc Glave PB, Kim T, Vallera DA, Goldman AI, Bostrom B, Hurd D and Ramsay MKC. Comparison of autologous and allogeneic bone marrow transplantation for treatment of highrisk refractory acute lymphoblastic leukemia. N Engl J Med 1987; 317: 461–467.

    PubMed  Google Scholar 

  8. Kimoto Y. and Taguchi T. Adoptive immunotherapy of malignant diseases with IL-2-activated lymphocytes. Biken J 1987; 30: 29–38.

    PubMed  Google Scholar 

  9. Kimoto Y, Tanji Y, Tanaka T and Taguchi T. Adoptive immunotherapy of malignant diseases using normal allogeneic LAK cells. Jpn J Cancer Chemother 1987; 14: 1884–89.

    Google Scholar 

  10. Kimoto Y, Tanaka T, Fujiwara A and Taguchi T. Influence of pokeweed mitogen on the proliferation and the cytotoxicity of LAK cells. Biother 1989; 3: 1045–1050.

    Google Scholar 

  11. Kimoto Y, and Taguchi T. Culture of allogeneic LAK cells: comparison of individually-cultured LAK cells and mixcultured LAK cells. Biother 1989; 3: 533–9.

    Google Scholar 

  12. Kimoto Y, Tanaka T, Fujiwarl A, Fujita M and Taguchi T. Enhancing effect of pokeweed mitogen on the proliferation and the cytotoxicity of lymphokine-activated killer cells. Jpn J Cancer Res 1992; 83: 631–7.

    PubMed  Google Scholar 

  13. Kohler PC, Hank JA, Exten R, Minkoff DZ, Wilson DG, and Sondel PM. Clinical response of a patient with diffuse histiocytic lymphoma to adoptive chemoimmunotherapy using cyclophsphamide and alloactivated haploidentical lymphocytes. A case report and phase I trial. Cancer 1985; 55: 552–560.

    PubMed  Google Scholar 

  14. Kohler PC, Hank JA, Minkoff DZ, and Sondel PM. Clinical adoptive chemoimmunotherapy with allogeneic alloactivated HLA-haploidentical lymphocytes: controlled induction of graft-versus-host-reactions. Cancer Immunol Immunother 1988; 26: 74–82.

    PubMed  Google Scholar 

  15. Malecker JR, Friddell CS, Sferruzza A, Thurman GB, Lewko WM, West WH, Oldham RK, and Yannelli JR. Activation and expansion of tumor-derived activated cells for therapeutic use. J Natl Cancer Inst 1989; 81: 1655–60.

    PubMed  Google Scholar 

  16. Ortaldo JR, Mason A and Overton R. Lymphokine-activated killer cells analysis of progenitors and effectors. J Exp Med 1986; 164: 1193–205.

    PubMed  Google Scholar 

  17. Phillips JH and Lanier LL. Dissection of the lymphokine-activated killer phenomenon: relative contribution of peripheral blood natural killer cells and T lymphocytes to cytolysis. J Exp Med 1986; 164: 814–25.

    PubMed  Google Scholar 

  18. Rosenberg SA, Lotze MT, Muul LM, Leitman S, Chang AE, Ettinghausen SE, Matory YL, Skibber JH, Shiloni E, Vetto JT, Seipp CA, Simpson C, and Reichert CM. Observation 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.

    PubMed  Google Scholar 

  19. Rosenberg SA, Spiess P and Lafreniere R. A new approach to the adoptive immunotherapy of cancer with tumor-infiltrating lymphocytes. Science 1986; 233: 1318–21.

    PubMed  Google Scholar 

  20. Rosenberg SA, Lotze MT, Muul LM, Chang AE, Avis FP, Leitman S, Linehan WM, Ribertson CN, Lee RE, Rubin JT, Seipp CA, Simpson CG, and White DE. 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: 889–97.

    PubMed  Google Scholar 

  21. Rosenberg SA, Packard BS, Aebersold PM, Solomon D, Topalian SL, Toy ST, Simon P, Lotze MT, Yang JC, Seipp CA, Simpson C, Carter C, Bock S, Schwartzentruber D, Wei JP and White DE. Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. A preliminary report. N Engl J Med 1988; 319: 1676–80.

    PubMed  Google Scholar 

  22. Tilden AB, Itoh K and Balch GM. Human-lymphokine-activated killer (LAK) cells:identification of two types of effecter cells. J Immunol 1987; 138: 1068–73.

    PubMed  Google Scholar 

  23. Topalian SL, Solomon D, Avis FP, Chang AE, Freerksen L, Linehan WM, Lotze MT, Robertson CN, Seipp CA, Simon P, Simpson CG and Rosenberg SA. Immunotherapy of patients with advanced cancer using tumor-infiltrating lymphocytes and recombinant interleukin-2: A pilot study. J Clin Oncol 1988; 6: 839–53.

    PubMed  Google Scholar 

  24. Topalian SL, Kasid A and Rosenberg SA. Immunoselection of a human melanoma resistant to specific lysis by autologous tumor-infiltrating lymphocytes. Possible mechanisms for immunotherapeutic failures. J Immunol 1990; 144: 4487–95.

    PubMed  Google Scholar 

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Kimoto, Y., Tanaka, T., Tanji, Y. et al. Use of human leukocyte antigen-mismatched allogeneic lymphokine-activated killer cells and interleukin-2 in the adoptive immunotherapy of patients with malignancies. Biotherapy 8, 41–50 (1994). https://doi.org/10.1007/BF01878120

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  • DOI: https://doi.org/10.1007/BF01878120

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