Summary
Various subpopulations of human leukocytes may be induced by lymphokines to exert cytotoxic activity. In man major histocompatibility complex non-restricted tumor cell lysis by interleukin-2 (IL-2) induced peripheral blood lymphocytes is attributed mainly to natural killer cells. These T cell receptor negative large granular lymphocytes are called lymphokine activated killer (LAK) cells. In order to explore the potential of LAK cells in tumor therapy, several clinical studies have been conducted, using IL-2 alone or in combination with ex vivo IL-2-activated peripheral blood lymphocytes. Objective responses have reproducibly been achieved only in renal cell carcinoma and malignant melanoma and were associated with considerable toxicity. In view of restricted efficacy and increasing doubts as to whether LAK cells indeed account for the in vivo observed responses, more recent strategies focus on tumor antigen specific cytotoxic T cells or tumor infiltrating lymphocytes. Successful translation of this approach into clinical practice, however, may be dependend on some basic problems of tumor immunology to be solved which were thought to be by-passed by the LAK cell approach.
Article PDF
Similar content being viewed by others
References
Anegon J, Cuturi MC, Trinchieri G, Perussia B (1988) Interaction of Fc receptor (CD 16) ligands induces transcription of interleukin 2 receptor (CD 25) and lymphokine genes and expression of their products in human natural killer cells. J Exp Med 167: 452–472
Aronson FR, Libbey P, Brandon EP, Janicka MW, Mier JW (1988) Interleukin 2 rapidly induces natural killer cell adhesion to human endothelial cells. A potential mechanism of endothelial injury. J Immunol 141: 158–168
Atkins MB, Gould JA, Allegretta M, Li JJ, Dempsey RA, Rudders RA, Parkinson DR, Reichlin S, Mier JW (1986) Phase I evaluation of recombinant interleukin-2 in patients with advanced malignant disease. J Clin Oncol 4: 1380–1391
Barlozzari T, Reynolds CW, Herberman RB (1983) In vivo role of natural killer cells: Involvement of large granular lymphocytes in the clearance of tumor cells in anti-asialo GM1-treated rats. J Immunol 131: 1024–1027
Berd D (1988) Immunotherapy of cancer using interleukin-2. Immunol Today 9: 193–194
Billaud M, Calender A, Seigneurin JM, Lenoir GM (1987) LFA-1, LFA-3, and ICAM-1 expression in Burkitt's lymphoma. Lancet II: 1327–1328
Borst J, van de Griend RJ, van Oostveen JW, Ang SL, Melief CJ, Seidman JG, Bolhuis RL (1987) A T-cell receptor gamma/CD3 complex found on cloned functional lymphocytes. Nature 325: 683–688
Breder CD, Dinarello CA, Saper CB (1988) Interleukin-1 immunoreactive innervation of the human hypothalamus. Science 240: 321–323
Cheever MA, Greenberg PD, Fefer A (1981) A specific adoptive therapy of established leukemia with syngeneic lymphocytes sequentially immunized in vivo and in vitro and non-specifically expanded by culture with interleukin 2. J Immunol 126: 1318–1326
Cheever MA, Thompson DR, Klarnet JP, Greenberg PD (1986) Antigen-driven long term cultured T cells proliferate in vivo, distribute widely, mediate specific tumor therapy, and persist long term as functional memory cells. J Exp Med 163: 1100–1112
Davis MM, Bjorkman P (1988) T-cell antigen receptor genes and T-cell recognition. Nature 334: 395–402
Dutcher JP, Creekmore S, Weiss GR, Margolin K, Markowitz AB, Roper MA, Parkinson D (1987) Phase II study of high dose interleukin-2 and lymphokine activated killer cells in patients with melanoma. Proc ASCO 6: 246 (abstr 970)
Ettinghausen SE, Lipford II EH, Mule JJ, Rosenberg SA (1985) Systemic administration of recombinant interleukin 2 stimulates in vivo lymphoid proliferation in tissues. J Immunol 135: 1488–1497
Ettinghausen SE, Moore JG, White DE, Platanias L, Young NS, Rosenberg SA (1987) Hematologic effects of immunotherapy with lymphokine activated killer cells and recombinant interleukin-2 in cancer patients. Blood 69: 1654–1660
Ettinghausen SE, Puri RK, Rosenberg SA (1988) Increased vascular permeability of organs mediated by the systemic administration of lymphokine-activated killer cells and recombinant interleukin-2 in mice. J Natl Cancer Inst 80: 177–188
Fefer A, Einstein AB, Cheever MA, Berenson JR (1976) Models for syngeneic adoptive chemoimmunotherapy of murine leukemias. Ann N Y Acad Sci 276: 573–582
Fisher RJ, 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 cell cancer treated with interleukin-2 and lymphokine activated killer cells. A phase I clinical trial. Ann Int Med 108: 518–523
Forni G, Giovarelli M, Santoni A, Modesti A, Forni M (1987) Interleukin-2 activated tumor inhibition in vivo depends on the systemic involvement of host immunoreactivity. J Immunol 138: 4033–4041
Fraser-Scott K, Hatzakis H, Seong D, Jones CM, Wu KK (1988) Influence of natural and recombinant interleukin 2 on endothelial cell archidonate metabolism. Induction of de novo synthesis of prostaglandin H synthase. J Clin Invest 82: 1877–1883
Gaynor ER, Vitek L, Sticklin L, Creekmore SP, Ferraro ME, Thomas Jr JX, Fisher SG, Fisher RI (1988) The hemodynamic effects of treatment with interleukin-2 and lymphokine-activated killer cells. Ann Intern Med 109: 953–958
Gemlo BT, Palladino MA, Jaffe HS, Espevik TP, Rayner AA (1988) Circulating cytokines in patients with metastatic cancer treated with recombinant interleukin 2 and lymphokine-activated killer cells. Cancer Res 48: 5864–5867
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: 1823–1841
Grimm EA, Ramsey KM, Mazumder A, Wilson DJ, Djeu JY, Rosenberg SA (1983) Lymphokine-activated killer cell phenomenon. II. Precursor phenotype is serologically distinct from peripheral T lymphocytes, memory cytotoxic thymus-derived lymphocytes, and natural killer cells. J Exp Med 157: 884–897
Grönberg A, Ferm MT, Reynolds CW, Ortaldo JR (1988) Interferon gamma treatment of K562 cells inhibits natural killer cell triggering and decreases the susceptibility to lysis by cytoplasmatic granules from large granular lymphocytes. J Immunol 140: 4397–4402
Herberman RB, Hiserodt J, Vujanovich N, Balch C, 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: 178–181
Herberman RB, Ortaldo SR, Bonnard GD (1979) Augmentation of interferon of human natural and antibody dependent cell mediated cytotoxicity. Nature 277: 221–223
Hercend T, Meuer S, Brennan A, Edson MA, Acuto O, Reinherz EL, Schlossman SF, Ritz J (1983) Identification of a clonally restricted 90 kD heterodimer on two human cloned natural killer cell lines. J Exp Med 158: 1547–1560
Hercend T, Griffin JD, Bensussan A, Schmidt RE, Edson MA, Brennan A, Murray C, Daley JF, Schlossman SF, Ritz J (1985) Generation of monoclonal antibodies to a human natural killer cell clone. Characterization of two natural killer-associated antigens, NKH 1a and NKH 2, expressed on subsets of large granular lymphocytes. J Clin Invest 75: 932–943
Herrmann F, Schmidt RE, Ritz J, Griffin JD (1987) In vitro regulation of human hematopoiesis by natural killer cells: analysis at a clonal level. Blood 69: 246–254
Hersey P, MacDonald MJ, Schibeci SD, Burns C (1986) Clonal analysis of cytotoxic T lymphocytes (CTL) against autologous melanoma. Classification based on phenotype, specificity and inhibition by monoclonal antibodies to T cell structures. Cancer Immunol Immunother 22: 15–23
Hersey P, Bolhuis R (1987) “Non-specific” MHC-unrestricted killer cells and their receptors. Immunol Today 8: 233–239
Huberman M, Mittelman A, Fallon B, Groopman J, Skelos S, Gafney E, Arlin Z, Hill J, Leung P, Levitt D (1988) Preliminary observations from a phase I study of recombinant interleukin-2 (IL-2) and Roferon A (recombinant human alpha-IFN) in patients with malignant B-cell disease, renal and colorectal cancer, and melanoma. Proc ASCO 7: 169 (abstr 653)
Itoh K, Tilden AB, Kumagai K, Balch CM (1984) Leu11 + lymphocytes with natural killer (NK) activity are precursors of recombinant interleukin 2 (rIL-2)-induced activated killer (AK) cells. J Immunol 134: 802–807
Jung G, Müller-Eberhard JH (1988) An in-vitro model for tumor immunotherapy with antibody heteroconjugates. Immunol Today 9: 257–260
Kasahara T, Djeu JY, Dougherty SF, Oppenheim JJ (1983) Capacity of human large granular lymphocytes (LGL) to produce multiple lymphokines: Interleukin 2, interferon, and colony stimulating factor. J Immunol 131: 2379–2385
Kedar E, Ikejiri BL, Timonen T (1981) Antitumor reactivity in vitro and in vivo of lymphocytes from normal donors and cancer patients propagated in culture with T-cell growth factor (TCGF). Eur J Cancer Clin Oncol 19: 757–773
Kedar E, Ikejiri BL, Gorelik E, Herberman RB (1982) Natural cell-mediated cytotoxicity in vitro and inhibition of tumor growth in vivo by murine lymphoid cells cultured with T cell growth factor (TCGF). Clin Immunol Immunother 13: 14–23
Kist A, Ho AD, Räth U, Wiedemann B, Bauer A, Schlick E, Kirchner H, Männel DN (1988) Decrease of natural killer cell activity and monokine production in peripheral blood of patients treated with recombinant tumor necrosis factor. Blood 72: 344–348
Kotasek D, Vercelotti GM, Ochoa AC, Bach FH, White JG, Jacob HS (1988) Mechanism of cultured endothelial injury by lymphokine-activated killer cells. Cancer Res 48: 5528–5532
Krigel RL, Padavic-Shaller KA, Rudolph AR, Litwin S, Konrad M, Bradley EC, Comis RL (1988) A phase I study of recombinant interleukin 2 plus recombinant beta-interferon. Cancer Res 48: 3875–3881
Kripke ML (1988) Immunoregulation of carcinogenesis: past, present, and future. J Natl Cancer Inst 80: 722–727
Lafreniere R, Rosenberg SA (1985) Adoptive immunotherapy of murine hepatic metastases with lymphokine activated killer (LAK) cells and recombinant interleukin 2 (rIL-2) can mediate the regression of both immunogenic and non-immunogenic sarcomas and adenocarcinomas. J Immunol 135: 4273–4280
Lanier LL, Le AM, Phillips JH, Warner NL, Babcock GF (1983) Subpopulations of human natural killer cells defined by expression of the Leu-7 (HNK-1) and Leu-11 (NK-15) antigens. J Immunol 131: 1789–1796
Lanier LL, Le AM, Civin CJ, Loken MR, Phillips JH (1986) The relationship of CD 16 (Leu 11) and Leu19 (NKH-1) antigen expression on human peripheral blood NK cells and cytotoxic T lymphocytes. J Immunol 136: 4480–4486
Lanier LL, Le AM, Cwirla S, Federspiel N, Phillips JH (1986) Antigenic, functional, and molecular genetic studies to human natural killer cells and cytotoxic T lymphocytes not restricted by the major histocompatibility complex. Fed Proc 45: 2823–2828
Lanier LL, Phillips JH (1986) Evidence for three types of human cytotoxic lymphocytes. Immunol Today 7: 132–134
Lanier LL, Buck DW, Rhodes DL, Ding A, Evans E, Barney C, Phillips JH (1988) Interleukin-2 activation of natural killer cells rapidly induces the expression and phosphorylation of the Leu 23 activation antigen. J Exp Med 167: 1572–1585
Lanzavecchia A (1986) Is the T cell receptor involved in T cell killing. Nature 319: 778–780
Lindemann A, Höffken K, Schmidt RE, Diehl V, Kloke O, Gamm H, Hayungs J, Oster W, Böhm M, Kolitz JE, Franks CR, Herrmann F, Mertelsmann RH (1989) A phase-II study of low dose cyclophosphamide and recombinant human interleukin-2 in metastatic renal cell carcinoma and malignant melanoma. Cell Immunol Immunother 28: 275–281
Lotze MT, Line BR, Mathisen DJ, Rosenberg SA (1980) The in vivo distribution of autologous human and murine lymphoid cells grown in T cell growth factor (TCGF): Implications for the adoptive immunotherayp of tumors. J Immunol 125: 1487–1493
Lotze MT, Grimm E, 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 161: 4420–4425
Lotze MT, Frana LW, Sharrow SO, Robb RJ, Rosenberg SA (1985) In vivo administration of purified human interleukin 2. J Immunol 134: 157–166
Lotzova E, Herberman RB (eds) (1986) Immunobiology of natural killer cells (Vols I & II). CRC Press, Boca Raton, Fla, USA
Marcus SL, Dutcher JP, Paietta E, Ciobanu N, Wiernik PH (1987) Plasma free catecholamines in patients during immunotherapy with high-dose interleukin-2 (IL-2). Proc AACR 28: 369 (abstr 1461)
McCoy JL, Herberman RB, Rosenberg EB, Donelly FC, Levine PH, Alford C (1973) 51Chromium release assay for cell-mediated cytotoxicity of human leukemia and lymphoid tissue culture cells. Natl Cancer Inst Monogr 37: 59–67
Mertelsmann R, Welte K, Sternberg C, O'Reilly R, Moore MA, Clarkson BD, Oettgen HF (1984) Treatment of immuno-deficiency with interleukin 2. J Biol Response Mod 4: 483–490
Meuer SC, Fitzgerald KA, Hussey RE, Hodgdon JC, Schlossman SF, Reinherz EL (1983) Clonotypic structures involved in antigen-specific human T cell function: relationship to the T 3 molecular complex. J Exp Med 157: 705–719
Mier J, Souza L, Allegretta M (1985) Dissimilarities between purified interleukin-1 and recombinant human interleukin-2 in the induction of fever, brain prostaglandin and acute phase protein synthesis. J Biol Response Mod 4: 35–42
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: 409–424
Moingeon P, Ythier A, Goubin G, Faure F, Novill A, Delmon L, Reinaud M, Forestier F, Doffos F, Bohoun C, Hercend T (1986) A unique T cell receptor complex expressed on human fetal lymphocytes displaying natural-killer like activity. Nature 323: 638–640
Morita T, Yonese Y, Minato N (1987) In vivo distribution of interleukin 2-activated autologous lymphocytes administered by intra-arterial infusion in patients with renal cell cancer. J Natl Cancer Inst 78: 441–447
Mule JJ, Shu S, Rosenberg SA (1985) The antitumor efficacy of lymphokine-activated killer cells and recombinant interleukin 2 in vivo. In Immunol 135: 646–652
Mule JJ, Smith CA, Rosenberg SA (1987) Interleukin 4 (B cell stimulatory factor 1) can mediate the induction of lymphokine aktivated killer cell activity derived against fresh tumor cells. J Exp Med 166: 792–797
Mule JJ, Young JC, Lafreniere RC, Shu S, Rosenberg SA (1987) Identification of cellular mechanisms operational in vivo during the regression of established pulmonary metastases by the systemic administration of high-dose recombinant interleukin-2. J Immunol 139: 285–294
Muul LM, Spiess PJ, Director EP, Rosenberg SA (1987) Identification of specific cytolytic immune responses against autologous tumor in humans bearing malignant melanoma. J Immunol 138: 989–995
Nagler A, Lanier LL, Phillips JH (1988) The effects of IL-4 on human natural killer cells. A potent regulator of IL-2 activation and proliferation. J Immunol 141: 2349–2351
Ortaldo JR, Mason A, Overton R, (1986) Lymphokine activated killer cells. Analysis of progenitors and effectors. J Exp Med 164: 1193–1205
Paciucci PA, Bhardwaj S, Odchimar R, Glidewell O, Holland JF (1988) Immunotherapy for metastatic cancer with recombinant interleukin-2 (rIL-2) by continuous infusion with and without adoptive cell transfer. Proc ASCO 7: 163 (abstr 630)
Perez P, Hoffman RW, Titus J, Segal DM (1986) Specific targeting of human peripheral blood T cells by heteroaggregates containing anti-T3 crosslinked to anti-target cell antibodies. J Exp Med 163: 166–178
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: 814–825
Phillips JH, Lanier LL (1986) Lectin-dependent and anti-CD 3 induced cytotoxicity are preferentially mediated by peripheral blood cytotoxic T lymphocytes expressing Leu 7 antigen. J Immunol 136: 1579–1585
Phillips JH, Lanier LL (1987) Acquisition of non-MHC restricted cytotoxic function by interleukin 2 activated thymocytes with an “immature” antigenic phenotype. J Immunol 139: 683–687
Phillips JH, Gemlo BT, Meyers 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
Ritz J, Campen TJ, Schmidt RE, Royer HD, Hussey RE, Reinherz EL (1985) Analysis of T-cell receptor gene rearrangement and expression in human natural killer cell clones. Science 228: 1540–1544
Rosenberg EB, Herberman RB, Levine PH, Halterman RH, McCoy IL, Wunderlich JR (1972) Lymphocyte cytotoxicity reactions to leukemia associated antigens in identical twins. Int J Cancer 9: 648–658
Rosenberg SA, Mule JJ, Spiess PJ, Reichert CM, Schwarz S (1985) Regression of established pulmonary metastases and subcutaneous tumor mediated by the systemic administration of high-dose recombinant interleukin 2. J Exp Med 161: 1169–1188
Rosenberg SA, Lotze MT, Muul LM, Leitman S, Chang AE, Ettinghausen SE, Matory YL, Skibber JM, Shilari 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. New Engl J Med 313: 1485–1492
Rosenberg SA, Spiess P, Lafreniere R (1986) A new approach to adoptive immunotherapy of cancer with tumor infiltrating lymphocytes. Science 223: 1318–1321
Rosenberg SA, Lotze MT, Muul LM, Chang AE, Avis FP, Leitman S, Linehan WM, Robertson CN, Lee RE, Rubin JT, Seipp CA, Simpson CG, 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. New Engl J Med 316: 889–879
Rosenberg SA (1988) Immunotherapy of cancer using interleukin 2: Current status and future prospects. Immunology Today 9: 58–62
Rosenberg SA (1988) Cancer therapy with interleukin-2: Immunologic manipulations can mediate regression of cancer in humans. J Clin Oncol 6: 403–406
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, White DE (1988) Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. N Engl J Med 319: 1676–1680
Ross GD, Cain JH, Lachmann PJ (1985) Membrane complement receptor type three (CR3) has lectin-like properties analogous to bovine conglutinin and functions as a receptor for zymosan and rabbit erythrocytes as well as a receptor for iC3b. J Immunol 134: 3307–3315
Salup RR, Wiltrout RH (1986) Treatment of adenocarcinoma in the peritoneum of mice: chemoimmunotherapy with interleukin-2 stimulated cytotoxic lymphocytes as a model for treatment of minimal residual disease. Cancer Immunol Immunother 22: 31–36
Scala G, Allavena P, Djeu JY, Kasahara T, Ortaldo JR, Herberman RB, Oppenheim JJ (1984) Human large granular lymphocytes are potent producers of interleukin-1. Nature 309: 56–59
Schendel DJ, Wank R, Bonnard GD (1980) Genetic specificity of primary and secondary proliferative and cytotoxic responses of human lymphocytes grown in conditioned culture. Scand J Immunol 11: 99–107
Schmidt RE, Bartley G, Levine H, Schlossman SF, Ritz J (1985) Functional characterization of LFA-1 antigens in the interaction of human NK clones and target cells. J Immunol 135: 1020–1025
Shinkai Y, Takio K, Okumura K (1988) Homology of perforin of the ninth component of complement (C9). Nature 334: 525–527
Siegel JP, Sharon M, Smith PL, Leonard WJ (1987) The interleukin-2 receptor beta-chain (p70): Role in mediating signals for LAK, NK, and proliferative activities. Science 238: 75–78
Siliciano RF, Pratt JC, Schmidt RE, Ritz J, Reinherz EL (1985) Activation of cytolytic T lymphocyte and natural killer function through the T11 sheep erythrocyte binding protein. Nature 317: 428–430
Simmons D, Seed B (1988) The Fc gamma receptor of natural killer cells is a phospholipid-linked membrane protein. Nature 333: 568–570
Smith KA (1988) Interleukin-2: Inception, impact and implications. Science 240: 1169–1176
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: 502–511
Sone S, Utsugi T, Nii A, Ogura T (1988) Differential effects of recombinant interferons alpha, beta and gamma on induction of human lymphokine (IL-2)-activated killer activity. J Natl Cancer Inst 80: 425–431
Sosman, JA, Kohler PC, Hank, J Moore KH, Bechhofer R, Storer B, Sondel PM (1988) Repetitive weekly cycles of recombinant human interleukin-2: Responses of renal cell cancer with acceptable toxicity. J Natl Cancer Inst 80: 60–63
Spits H, Yssel H, Poliard X, Kastelein R, Figdor C, De-Vries JE (1988) Interleukin-4 inhibits interleukin-2 mediated induction of human lymphokine-activated killer cells, but not the generation of antigen-specific cytotoxic T lymphocytes in mixed leukocyte cultures. J Immunol 141: 29–36
Talmadge JE, Phillips JH, Schindler J, Tribble H, Pennington R (1987) Systematic preclinical study on the therapeutic properties of recombinant human interleukin 2 for the treatment of metastatic disease. Cancer Res 47: 5725–5732
Thompson JA, Lu DJ, Lindgren CG, Benz LA, Collins C, Levitt D, Fefer A (1988) Influence of dose and duration of infusion of interleukin-2 on toxicity and immunomodulation. J Clin Oncol 6: 669–678
Timonen T, Ranki A, Saksela E, Häyry P (1979) Human natural-cell mediated cytotoxicity against fetal fibroblasts. III. Morphological and functional characterization of the effector cells. Cell Immunol 48: 121–132
Topalian SL, Solomon D, Avis FP, Chang AE, Freerksen DL, Linehan WM, Lotze MT, Robertson CN, Seipp CA, Simon P, Simpson CG, Rosenberg SA (1988) Immunotherapy of patients with advanced cancer using tumor infiltrating lymphocytes and recombinant interleukin-2: A pilot study. J Clin Oncol 6: 839–853
Trinchieri G, Matsumoto-Kubayashi M, Clark SC, Seehra J, London L, Perussia B (1984) Response of resting human peripheral blood natural killer cells to interleukin 2. J Exp Med 160: 1147–1169
Tschopp J, Schafer S, Masson D, Peitsch MC, Heusser C (1989) Phosphorylcholine acts as a Ca-dependent receptor molecule for lymphocyte perforin. Nature 337: 272–274
Uchida A, Micksche M (1983) Lysis of fresh human tumor cells by autologous large granular lymphocytes from peripheral blood and pleural effusions. Int J Cancer 32: 37–44
Uchiyama T, Broder S, Waldman TA (1981) A monoclonal antibody (anti-TAC) reactive with activated and functionally mature human T cells. I Production of anti-TAC monoclonal antibody and distribution of TAC(+) cells. J Immunol 126: 1393–1397
Vetto JT, Papa MZ, Lotze MT, Chang AE, Rosenberg SA (1987) Reduction of toxicity of interleukin-2 and lymphokine-activated killer cells in humans by the administration of corticosteroids. J Clin Oncol 5: 496–503
Wagstaff J, Goey SH, Scheper RJ, Vermorken JB, van der Hoeven JJM, Swartzmann G, Bijvank EM, Veenhof CHN, Pinedo HM (1988) A phase I study of sequential recombinant interferon gamma and recombinant interleukin-2 in patients with solid tumors. Proc ASCO 7: 168 (abstr 651)
Wang J, Walle A, Gordon B, Novogrodsky A, Suthanthiran M, Rubin AL, Morrison H, Silver RT, Stenzel KH (1987) Adoptive immunotherapy for stage IV renal cell carcinoma: A novel protocol utilizing periodate and interleukin-2 activated autologous lymphocytes and continuous infusions of low dose interleukin-2. JAMA 83: 1016–1023
Weber J, Joy G, Tanaka K, Rosenberg SA (1987) Immunotherapy of a murine tumor with interleukin 2. Increased sensitivity after MHC class I gene transfection. J Exp Med 166: 1716–1733
West WH, Tauer KW, Yanelli JR, Marshall GD, Orr DW, Thurman GB, Oldham RK (1987) Constant infusion recombinant interleukin-2 in adoptive immunotherapy of cancer. N Engl J Med 316: 898–905
Winkelhaake JL, Stampfl S, Zimmermann RJ (1987) Synergistic effects of combination therapy with human recombinant interleukin 2 and tumor necrosis factor in murine tumor models. Cancer Res 47: 3948–3953
Young JD-E, Liu C-C (1988) Multiple mechanisms of lymphocyte mediated killing. Immunology Today 9: 140–144
Zalman LS, Brothers MA, Chin FJ, Müller-Eberhard HJ (1986) Mechanism of cytoxicity of human large granular lymphocytes: relationship of the cytotoxic lymphocyte protein to the ninth component (C9) of human complement. Proc Natl Acad Sci USA 83: 5262–5266
Zarcone D, Prasthofer EF, Malavasi F, LoBuglio AF, Grossi CE (1987) Ultrastructural analysis of human natural killer cell activation. Blood 69: 1725–1736
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Lindemann, A., Herrmann, F., Oster, W. et al. Lymphokine activated killer cells. Blut 59, 375–384 (1989). https://doi.org/10.1007/BF00321208
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00321208