Summary
Five patients with hepatocellular carcinoma were subjected to immunotherapy: three patients were treated by adoptive immunotherapy with lymphokine-activated killer (LAK) cells and recombinant interleukin-2 (rIL-2), and two patients by systemic administration of rIL-2 alone. In one patient with diffuse-type hepatocellular carcinoma and portal vein thrombosis who was treated by infusion of LAK cells (a total number of 1.5x1010 cells/13 doses) and continuous rIL-2 administration (a total dose of 1.25x108 units) via a percultaneously placed hepatic arterial catheter, the size of the tumor reduced dramatically and the portal vein thrombosis retracted. In two patients who had LAK cells infused (totals of 6.6x109 cells/4 doses and 3.1x109 cells/2 doses, respectively) during hepatic angiogram followed by systemic administration of rIL-2 twice a day, no clinical improvement was noticed. In two patients who received rIL-2 alone systemically (total doses of 8.9x107 and 5.5x107 units, respectively), neither clinical improvement nor severe side effects were observed. The results suggest that adoptive immunotherapy combined with continuous local administration of rIL-2 via a percutaneously placed hepatic arterial catheter may be an effective therapy without apparent side effects for patients with hepatocellular carcinoma who cannot be treated by conventional cancer therapy.
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Alexander JJ, Bey EM, Geddes EM, Lecatsas G (1976) Establishment of a continuously growing cell line from primary carcinoma of the liver. S Afr Med J 50:2124–2128
Chang AE, Hyatt CL, Rosenberg SA (1984) Systemic administration of recombinant human interleukin-2 in mice. J Biol Response Mod 3:561–572
Donohue JH, Rosenberg SA (1983) The fate of interleukin-2 after in vivo administration. J Immunol 130:2203–2208
Ettinghausen SE, Rosenberg SA (1986) Immunotherapy of murine sarcemas using lymphokine activated killer cells: optimization of the schedule and route of administration of recombinant interleukin-2. Cancer Res 46:2784–2792
Grinm 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 blood lymphocytes. J Exp Med 155:1823–1841
Itoh K, Tilden AB, Balch CM (1986) Lysis of human solid tumor cells by lymphokine-activated natural killer cells. J Immunol 136:3910–3915
Jacobs SK, Wilson DJ, Kornblith PL, Grimm EA (1986) Interleukin-2 and autologous lymphokine-activated killer cells in the treatment of malignant glioma. A preliminary report. J Neurosurg 64:743–749
Kedar E, Weiss DW (1983) The in vitro generation of effector lymphocytes and their employment in tumor immunotherapy. Adv Cancer Res 38:171–287
Lafreniere R, Rosenberg SA (1985) Adoptive immunotherapy of murine hepatic metastases with lymphokine activated killer (LAK) cells and recombinant interleukin 2 (RIL2) can mediate the regression of both immunogenic and nonimmunogenic sarcomas and an adenocarcinoma. J Immunol 135:4273–4280
Lotze MT, Grimm EA, Mazumder A, Strausser JL, Rosenberg SA (1981) Lysis of fresh and cultured autologous tumor by human lymphocytes cultured in T-cell growth factor. Cancer Res 41:4420–4425
Lotze MT, Matory YL, Ettinghausen SE, Rayner AA, Sharrow SO, Seipp CAY, Custer MC, Rosenberg SA (1985) In vivo administration of purified human interleukin 2. II. Half life and immunologic effects, and expansion of peripheral lymphoid cells in vivo with recombinant IL 2. J Immunol 135:2865–2875
Mazumder A, Eberlein TJ, Grimm EA, Wilson DJ, Keenan AM, Aamodt R (1984) Phase I study of the adoptive immunotherapy of human cancer with lectin-activated autologous mononuclear cells. Cancer 53:896–905
Mule JJ, Shu S, Schwarz SL, Rosenberg SA (1984) Adoptive immunotherapy of established pulmonary metastases with LAK cells and recombinant interleukin-2. Science 225:1487–1479
Mule JJ, Shu S, Rosenberg SA (1985) The anti-tumor efficacy of lymphokine-activated killer cells and recombinant interleukin-2 in vivo. J Immunol 135:646–652
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 55:1327–1333
Rosenberg SA (1984a) Adoptive immunotherapy of cancer: accomplishment and prospects. Cancer Treat Rep 68:233–255
Rosenberg SA (1984b) Immunotherapy of cancer by systemic administration of lymphoid cells plus interleukin-2. J Biol Response Mod 3:501–511
Rosenberg SA, Lotze MT, Muul LM, Leitman S, Chang AE, Ettinghausen SE, Matory YL, Skibber JM, Shiloni E, Vetto JT, Seipp CA, Simpson C, Reichert CM (1985) Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2 to patients with metastatic cancer. N Engl J Med 313:1485–1492
Watkins E Jr, Khazei AM, Khalil SN (1970) Surgical basis for arterial infusion chemotherapy of disseminated carcinoma of the liver. Surg Gynecol Obstet 130:581–605
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Ishikawa, T., Imawari, M., Moriyama, T. et al. Immunotherapy of hepatocellular carcinoma with autologous lymphokine-activated killer cells and/or recombinant interleukin-2. J Cancer Res Clin Oncol 114, 283–290 (1988). https://doi.org/10.1007/BF00405835
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DOI: https://doi.org/10.1007/BF00405835