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Interleukin-2 in cancer therapy: recent advances

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Pages 597-619 | Published online: 03 Mar 2008

References

  • OSENBERG SA, LOTZE M, CHANG AE, AVIS FP, LEITMANN S, LINEHAN WM, ROBERTSON CN, LEE RE, RUBIN JT, SEIPPCA, SIMPSON CG, WHITE DE: A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleulcin-2 or high-dose interleukin-2 alone. N. Engl. J. Med. (1987) 316:889–897.
  • ATZPODIEN j, KöREER A, FRANKS CR, POLIWODA KIRCHNER H: Home therapy with recombinant inter-leukin-2 and interferon-alpha2b in advanced human malignancies. The Lancet (1990) 335:1509–1512.
  • ROSENBERG SA, LOTZE M, MUUL L: Observation on the systemic administration of autologous lympholcine-ac-tivated killer cells and recombinant interleukin-2 to patients with metastatic cancer. N Engl. J. Med. (1985) 313:1485–1492.
  • STEIN RC, MALKOVSKA V, MORGAN S, GALAZKA A, AN-ISZEWSKI C, ROY SE, SHEARER Rj, MARSDEN RA, BEVAN SD, GORDON-SMTTH EC, COOMBES RC: The clin1rn1 effects of prolonged treatment of patients with advanced can-cer with low-dose subcutaneous interieukin 2. Br. J. Cancer (1991) 63:275–279.
  • WEST WH, TAUER KW, YANNELLI JR, MARSHALL GD, ORR fre.DW, THURMAN GB, OLDHAM RK: Constant infusionrecombinant interleuldn-2 in adoptive immunotherapy of advanced cancer. N. Engl. J. Med. (1987) 316:898–905.
  • FIETCHER M, GOLDSTEIN AL: Recent advances in the understanding of the biochemistry and pharmacology of interleukin-2. Lympbokine Res. (1987) 6:45–57.
  • SMITH KA: Interleukin-2: Inception, impact, and impli-cations. Science (1988) 240:1169–1182.
  • MORGAN DA, RUSCETTI FW, GALLO RC: Selective in vitrogrowth of T lymphocytes from normal human bone marrows. Science (1976) 192:1007–1012.
  • RUSCETTI FW, MORGAN DA, GALLO RC: Functional and morphologic characterization of human T cells con-tinuously grown in vitro. J. Immunol. (1977) 119:131–140.
  • GILLIS S, FERM MM, OU W, SMITH KA: T-cell growth-fac- ton Parameters of production and a quantitative mi-croassay for activity. J. Immunol. (1978) 120:2027–2031.
  • ROSENBERG SA: The development of new immuno-therapies for the treatment of can using interleukin-2. Ann. Surg. (1985) 208:121–135.
  • GRIMM EA, MAZUMDER A, ZHANG HZ, ROSENBERG SA:Lymphokine-activated killer cell phenomenon. J. Exp. Med. (1982) 155:1823–1841.
  • LOTZE MT, GRIMM EA, MAZUMDER EA, STAUSSER ROSENBERG SA: Lysis of fresh and cultured autologous tumor by human lymphocytes cultured in T-cell-growth factor. Cancer Res. (1981) 41:4420–4425.
  • HESLOP HE, GOTTLIEB DJ, BIANCHI ACM, MEAGER EA,PRENTICE HG, MEHTA AB, HOFFBRAND AV, BRENNER AK: In vivo induction of gamma interferon and tumor necrosis factor by interleukin-2 infusion following in-tensive chemotherapy or autologous marrow bone transplantation. Blood (1989) 74:1374–1380.
  • OH-SHI T, GOLDMAN CK, MISTI J, WALDMANN TA: TheInteraction of interleukin-2 with its receptor in the generation of suppressor T cells in the antigen-specific and antigen-nonspecific system in vitro. Clin. Immunol. Immunopathol. (1989) 52:447–459.
  • WANG H, SMITH K: The interleukin-2 receptors. J. EXP.Med. (1987) 166:1055–1069.
  • WALDMANN T: The IL-211L-2- receptor system: a targetfor rational immune intervention. Immunol. Today (1993) 14:264–270.
  • NOGUCHI M, YOSHIAKI N, RUSSEL SM, ZIEGLER SF,TSANG M, CAO X, LEONARD WJ: Interleukin-2 receptor gam.ma-rhain a functional component of the Inter-leukin-7 receptor. Science (1993) 262:1877–1880.
  • RUSSEL SM, ICEEGAN AD, HARADA N, NAKAMURA Y, NOGUCHI M, LELAND P, ET AL.: Interleukin-2 receptor gamma-chain: a functional component of the Inter-leukin-4 receptor. Science (1993) 262:1880–1883.
  • LISSONI P, BARNI S, ROVELLI F, TANCINI G: Lower sur-vival in metastatic cancer patients with reduced inter-leukin-2 blood concentrations Oncology (1991) 48:125–127.
  • RICHARDS JM, MICK R, LATTA J, DALY K, RATAIN M,VARDIMAN J, GOLOMB HJ: Serum soluble interleukin-2 receptor is associated with clinical and pathological disease status in hairy cell leukemia. Blood (1990) 76: 1941-1945.
  • LOTZOVA E, SAVARY C, KEATING M: Studies on the mechanism of defective natural killing in leukemia-dis-eased patients. Exp. Hematol. (1982) 10:83–88.
  • PHILLIPS JH, GEMLO BT, MYERS WW, RAYNER AA, LANIERII: In vivo and in vitro activation of natural killer cells In advanced cancer patients undergoing combined re-combinant interleukin-2 and LAK cell therapy. J. Clin. Oncol. (1987) 5:1933–1941.
  • WALE WSKI J, PAIETTA E, DUTCHER J, WIERNIK PH: Evalu-ation of natural killer and lymphokine-activated killer (LAX) cell activity in vivo in patients treated with high-dose interleukin-2 and adoptive transfer of autolo-gous LAX cells. J. Cancer Res. Clin. Oncol. (1989) 115:170–174.
  • BOLDT DH, MILLS BJ, GEMLO BT, HOLDEN H, MIER J,PAIETTA E, MCMANNIS JD, ESCOBEDO LV, SNIECINSKI I, RAYNER AA, HAWKINS MJ, ATKINS MB, CIOBANU N, ELLIS TM: Laboratory correlates of adoptive imtnunotherapy with recombinant interleukin-2 and lymphikine-acti-vated killer cells In humans. Cancer Res. (1988) 48:4409–4416.
  • GROSSMAN Z, HERBERMAN RB: Natural killer cells and their relationship to T cells: Hypothesis on the role of T cell receptor gene rearrangement on the course of adoptive differentiation. CancerRes. (1986) 46:2651–2658.
  • ROSENBERG SA, LOTZE MT, MULE JJ: New approaches to the immunotherapy of cancer using interleukin-2. Ann. Intern. Med. (1988) 108:853–864.
  • CLARK JW, SMITH J‘117, STEIS RG, URBA WJ, CRUM W, MILLER R, MCKNIGHT J, BEMAN JA, STEVENSON HC, CREEKMORE S, STEWART M, CONLON K, SZNOL M, KRE-MERS P, COHEN P, LONGO DL: Interleukin-2 and lym-phokine-activated killer cell therapy: Analysis of a bolus interleukin-2 and a continuous infusion inter-leukin-2 regimen. Cancer Res. (1990) 59:7343–7350.
  • ATZPODIEN J, KIRCHNER H: Cancer, cytokines, and cytotoxic cells: Interleukin-2 in the immunotherapy of human neoplasms. lain Wochenschr (1990) 68:1–11.
  • KANZ L, BRUGGER W, BROSS K, MERTELSMANN R: Com- bination of cytokines: Current status and future pros-pects. Br.J. Hematol. (1991) 79:96–104.
  • FARRAR J, BENJAMIN W, HILFIKER M, HOWARD M, FARRAR W, FULLER-FARRAR J: The biochemistry, biology, and role of interleukin-2 in the induction of cytotoxic T-cell and antibody forming B cell responses. Immunol. Rev. (1982) 63:129–166.
  • GRACOMINI P, AGUZZI A, PESTKA S: Modulation by recombinant DNA leukocyte (alpha) and fibroblast (beta) interferons of the expression and shedding of HELA and tumor-associated antigens by human mela-noma cells. J. Immunol. (1984) 133:1649–1655.
  • STI51 ihR H, WIEBKE E, TOMITA 5, BEIIDEGRUN A, TOPALIAN S, ROSENBERG SA, LOTZE M: Cytokines alter target cell susceptibility to lysis. J. Immunol. (1989) 142:1767–1773.
  • BARTH N, GALAZKA A, RUDNICK S: Lymphokines and cytokines. In: Princpes of Cancer Biotherapy. Oldham R (Ed) New York (Raven) 1988, p273–290.
  • W1EBICE E, ROSENBERG SA, LOTZE M: Acute immu-nologic effects of interleukin-2 therapy in cancer pa-tients. J. Clin. Oncol. (1988) 6:1440–1449.
  • KIM B, STEIN S, WARNAKA P, FRANCESCHI D: Enhanced in vivo therapy of pulmonary metastases with inter-feron and interleukin. j Surg. Res. (1988) 45:66–73.
  • PRUMMER O FRIC1CHOFEN N, DIGEL W, HEIMPEL H, PORZSOLT F: Spontaneous interferon- alpha antibodies In a patient with pure red cell aplasia and recurrent cutaneous carcinomas. Ann. Hematol. (1991) 62:76–80.
  • VON WUSSOW P, FREUND M, BLOCK B, DIEDRICH H, POLIWODA H, DEICHER H: Clinir21 significance of anti-IFN-alpha antibody titres during interferon therapy. The Lancet (1987) 2:635–636.
  • ATZPODIEN j, KORFER A, EVERS P, FRANKS CR, KNUVER-HOPE J, LOPEZ-HANNINEN E, DALLMANN I, HADAM M, POLIWODA H, KIRCHNER H: Low-dose subcutaneous recombinant interleukin-2 in advanced human malig-nancy: A phase U outpatient study. Mol. Bioth. (1990) 2:18–26.
  • FIGLIN RA, BELLDEGRUN A, MODAWER N, ZEFFREN J,DEKERNION J: Concomittant administration of recom-binant human interleukin-2 and recombinant inter-feron-alpha 2a: An active outpatient regimen in metastatic renal cell carcinoma. J. Chn. Oncol. (1992) 10:414–421.
  • LOPEZ-HANNINEN E, KORFER A, HADAM Al, SCHNEEK-LOTH C, DALLMANN I, MENZEL T, KIRCHNER H, POLI-WODA H, ATZPODIEN J: Biological monitoring of low-dose interleukin-2 in humen: Soluble interleukin-2 receptors, cytokines, and cell surface phenotypes. Can-cer Res. (1991) 50:6312–6316.
  • SOSMAN JA, KOHLER PC, HANK JA, SONDEL PM: Repeti-tive weekly cydes of interleukin-2. Clinical and immu-nologic effects of dose, schedule, and addition of indomethadn. J. Natl. Cancer Institute (1988) 80:1451–1461.
  • THOMPSON JA;LEE DJ, LINDGREN CG, BENZ LA, COLLINS C, LEVITT D, FEFER A: Influence of dose and duration of interleukin-2 on toxicity and immunomodulation. J. Clin. Oncol. (1988) 6:669–678.
  • NEGRIER S, PHILIP T, STOTER G, FRANKS CR: Interleukin-2 with or without lak cells in metastatic renal cell carcinoma: A report of a European multicenter study. Europ. J. Cancer Clin. Oncol. (1989) 25:21–28.
  • GAYNOR ER, WEISS GR, MARGOLIN ICA, ARONSON FR, SZNOL M, DEMCHAK P, GRIMA KM: Phase I study of high dose continuous infusion recombinant interkukin-2 and autologous lymphokine-activated killer cells in patients with metastatic or unresectable malignant melanoma and renal cell carcinoma. J. Natl. Cancer Institute (1990) 82:1397–1402.
  • ROSENBERG SA, LOTZE MT, YANG JC, TOPALIAN SL, CHANGE, SCHWARTZENTRUBER DJ, AEBERSOLD P, LETT-MAN S, LINEHAM WM, SEIPPC, WHITE DE, STEINBERG SM: Prospective randomized trial of high-dose interleukin-2 alone or in conjunction with lymphokine-activated killer cells for the treatment of patients with advanced cancer. J. Natl. Cancer Institute (1993) 85:622–631.
  • OLDHAM R, CHURCH C, ARNOLD J: Cancer Biotherapy: Insights into activated cellular therapy. Proc. Am. Soc. Clin. Oncol. (1993) 12:962.
  • PALMER PA, VINKE J, EVERS P, POURREAU C, OSICAM R:Continuous infusion of recombinant interleukin-2 with or without autologous lymphokine-activated killer cells for the treatment of advanced renal cell carcinoma. Europ. J. Cancer (1992) 28a:1038–1044.
  • MCCABE MS, STABLEIN D, HAWICINS MJ: The modifiedgroup c experience- phase HI randomized trials of IL-2 vs IL-2/IAK in advanced renal cell carcinoma and ad-vanced melanoma. Proc. Am. Soc. Clin. Oncol. (1991) 10:714.
  • RIVOLTINI L, ARIENTI F, BELLI F, GAMBOCORTI-PASSERINI C, CASCINELLI N: In vitro preferential lysis of autologous melanoma by tumor infiltrating lymphocytes (TIE). Association with clinical response after immuno-therapy with TIL and IL-2. Proc. Amer. Soc. Cancer Res. (1992) 33:1943.
  • BUKOWSKI RM, MCLAIN D, OLENCKI T, BUDD GT, MUR-THY SA: Interleukin-2: use in solid tumors. Stem Cells (1993) 11:6–32.
  • DUTCHER JP, CREEKMORE S, WEISS GR, ATICINS MB: Aphase II study of interleukin-2 and IAK cells in patients with metastatk malignant melanoma. J. Clin. Oncol. (1989) 7:477–485.
  • VAGLINI M, AMMATUNA M, ARIENTI F, PARMIANI G, PRADA A, SANTINAMI M, SANTORO N, BELLI F: Treatment of in transit metastases from cutaneous melanoma by Isolation perfusion in extra-corporeal circulation with interleukin-2 and lymphokine-activated killer cells. Proc. Am. Soc. Clin. Oncol. (1993) 13:1324.
  • ROSENBERG SA, SCHWARZ SL, SPIESS PJ: Combination immunotherapy for cancer: Synergistic antitumor in-teractions of interleukin-2, alpha-interferon, and tu-mor-infiltratin,g lymphocytes. J. Natl. Cancer Institute (1988) 80:1393–1397.
  • ROSENBERG SA, LOTZE MT, YANG JC, AEBERSOLD PM, LINEHAN WM, SEIPP CA, WHITE DE:Experience with the use of high-dose interleukin-2 in the treatment of 652 cancer patients. Ann. Surg. (1989) 210:474–485,
  • ROSENBERG SA, LOTZE MT, YANG YC, LINEHAN WM, SEIPP C, CALABRO S, KARP SE, SHERRY RM, STEINBERG S, WHITE DE: Combination therapy with interleukin-2 and alpha - interferon for the treatment of patients with advanced cancer. J. Clin. Oncol. (1989) 7:1863–1874.
  • WEISS GR, MARGOLIN KA, ARONSON FR, SZNOL M, AT-KINS MB, DUTCHER JP: A randomized phase II trial of continuous infusion interleukin-2 or bolus injection interleukin-2 plus lymphokine-activated killer cells for advanced renal cell carcinoma. J. Clin. Oncol. (1992) 10: 275–281.
  • ATZPODIEN J, KIRCHNER H: The out-patient use of re-combinant human interleukin-2 and interferon-alpha-2b in advanced malignancies. Europ. J. Cancer (1991) 27:88–92.
  • ROOK AH, ICEHRL JH, WAKEFIELD AM, ROBERTS AB, SPORN MB, BURLINGTON BD, LANE CH, FAUCI AS: Effects of transforming growth factor 0 on the functions of natural killer cells: Depressed cytolytic activity and blunting of interferon responsiveness. J. Immunol. (1986) 136:3916–3920.
  • SPORN MB, ROBERT AB, WAKEFIELD AM, ASSOIAN RK: Transforming growth factor 13: biological function and chemical structure. Science (1986) 233:532–534.
  • WAHL SM, HUNT DA, WONG HL, DOUGHERTY S, MCCARTNEY F, WAHL LM, ELLINGSWORTH L, SCHMIDT JA, GALL G, ROBERTS AB, SPORN MB: Transforming growth factor 13 is a potent inimunosuppressive agent that inhibits IL-1 dependent lymphocyte proliferation. J. Immunol. (1988) 40:3026–3032.
  • CUFFMAN RL, OHARA J, BOND MW, CARTY J, ZLOTNICK E, PAUL WE: B cell stimulatory factor-1 enhances the IgE response to liposaccharide-activated B cells. J. Immunol. (1986) 136:4538–4541.
  • ICARRAY S, DEFRANCE T, MERLE-BERM H, BANCHEREAU J, DEBRE P, GALANAUD P: Interleukin-4 counteracts the interleukin-2 induced proliferation of monoclonal B cells. J. Exp. Med. (1988) 168:85–97.
  • GALLAGHER G, WILCOX F, ALL-AZZAWI F: Interleukin-3 and interleukin-4 each strongly inhibit the induction and function of human LAK cells. am. Exp. Immunol. (1988) 74:166–170.
  • GEROSA F, TOMMASI M, GEROSA M, TRIDENTE G: Humanrecombinant interleukin-4 inhibits lymphokine-acti-vated killer activity of sheep erythrocyte rosette-form-ing and non-forming human lymphocytes. Intern. J. Cancer (1988) 42:902–905.
  • KAWAICAMI Y, ROSENBERG SA, LOTZE MT: Interleukin-4promotes the growth of tumor-infiltrating lymphocytes cytotoxic for human autologous melanoma. J. Exp. Med. (1988) 168:2183–2191.
  • LYNCH DH, NAMEN AE, MTH FR RE: In vivo evaluation ofthe effects of interleukirt-2, -4, and -7 on enhancing the inununotherapeutic efficiacy of antitumor cytotoxic T lymphocytes. Europ. j Immunol. (1991) 21:2977–2985.
  • MOSMANN TR, BOND MW, COFFMAN RL, OHARA J, PAUL WE: T cell and mast cell lines respond to B cell stimula-tory factor-1. Proc. Nat. Acad. Sci. USA (1986) 83:5654.
  • SPLAWSKI JB, JELINEK DF, LIPSKY PE: In3munomudula-tory role of IL-4 on the secretion of Ig by human B cells. J. Immunol. (1986) 142:1569–1575.
  • WIDMER MB, ACRES BR, SASSENFELD HM, GRABSTEIN KH: Regulation of cytolytic cell populations from human peripheral blood by B cell stimulatory factor-1 (inter-leukin-4).1 Exp. Med. (1987) 166:1447–1455.
  • NETAJI B, MURTHY S, BUDD GT, FINKE J, HERZOG P, STANLEY J, SERGI J, TUBBS R, BAUER L, BUKOWSKI EM: Phase IA/13 trial of interleukin-2 and interleukin-4 on refractory malignancy: Toxicity and immunologic changes: Proc. Am. Assoc. Cancer Res. (1991) 32:193.
  • HARANAKA K, SATOMI N, SAKURAI A: Antitumor activity of tumor necrosis factor against transplantable murine tumors and heterotransplanted human tumors in nude mice. Intern. J. Cancer (1984) 34:263–267.
  • OSTENSEN ME, THIELE DL, LIPSKY PE: Tumor necrosis factor-alpha enhances cytolytic activity of human natu-ral killer cells. J. Immunol. (1987) 138:4185–4191.
  • RANGES GE, FIGARI IS, ESPEVIK T, PALLADINO MA: Inhi-bition of cytotoxic T cell development by transforming growth factor and reversal by recombinant tumor ne-crosis factor. J Exp. Med. (1987) 166:991–998.
  • YANG SC, GRIMM EA, PARKINSON DR, CARINHAS J, FRY KD, MENDIGUREN-RODRIGUEZ A, LICCIARDELLO J, OWEN-SCHAUB LB, HONG WK, ROTH JA: Clinical and inununomodulatory effects of combinant irrumuno-therapy with low-dose interleulcin-2 and tumor ne-crosis factor-alpha in patients with advanced non-small cell lung cancer: A phase I triaL Cancer Res. (1991) 51:3669-3676.
  • PHILIP T, NEGRIER S, LASSET C, CORONEL B, BEET M, BLAY JY, MERROUCHE Y, CARRIE C, KAEMMERLEN P, CHAUVIN F, FAVROT M, OSKAM R, TABAH I, CLAVEL M, MOSKOVTCHENKO JF, MERCATELLO A: Patients with metastatic renal carcinoma candidate for immuno-therapy with cytokines. Analysis of a single institution study on 181 patients. Br. J. Cancer (1993) 68:1036–1042.
  • ITOH K, SHIIBA K, SHIMIZU Y, SUZUKI R, KUMAGAI K: Generation of activated killer cells by recombinant interleukin-2 in colaboration with gamma-interferon. J. Immunol. (1985) 134:3124–3129.
  • KOEFFLER HP, RANYARD J, YELTON L: Gamma-inter-feron induces expression of ILLA-D antigen on normal and leukemic human myeloid cells. Proc. Nat. Acad. Science USA (1984) 81:4080–4084.
  • MURRAY JL, PILLOW JK, ROSENBLUM MG: Differential invitro effects of alpha recombinant interferon and gamma recombinant interferon on the expression of melanoma-associated antigens. Proc. Am. Assoc. Cancer Res. (1986) 27:313.
  • NATHAN CF, MURRAY HW, WIEBE ME: Identification of Interferon- gamma as the lymphokine that activates human macrophage oxidative metabolism and antimi-crobial activity. J. Exp. Med. (1983) 158:670–689.
  • OTTESEN SS, AHRENKLEL V, KIELER J: Recombinant hu-man gamma- interferon exerts an antiproliferative ef- fect and modulates the expression of human leuko-cytes antigens A, B, C, and DR. Cancer Immunol. Immu-not& (1990) 31:93–98.
  • PACE JL, RUSSELL SW, TORRES BA, JOHNSON HM, GRAY PW: Recombinant mouse gamma-interferon induces the priming step in macrophage activation for tumor cell killing. j Immunol. (1983) 130:2100–2013.
  • RAWLINSON L, DALTON BJ, ROGERS K, REES RC: The Influence of interferon, alfa and gamma, singly or in combination on human natural cell mediated cytotoxic-ity. Biosci. Rep. (1988) 9:549–556.
  • BAARS JW, VAGSTAFF J, HOVEN E, VERMORKEN JB, VAN GROENINGEN CJ, SCHEPER RJ, FONK JCM, NIJMAN HW, FRANKS CR, DAMSMA O RINEDO HM: Phase I study on the sequential administration of recombinant human gamma-interferon and recombinant human inter-leukin-2 in patients with metastatic solid tumors./ Natl. Cancer Institute (1991) 83:1408–1410.
  • FARACE F, MATHIOT C, BRANDELY M, TURSZ T, DORVAL T, POUILLART P, TRIEBEL F, HERCEND T, FRIDMAN WH: Phase I trial with recombinant interleukin-2: Immune activationby riL-2 alone or following pretreatment with recombinant gamma-Interferon. Clin. Exp. Immunol. (1990) 82:194–199.
  • REDMAN BG, FLAHERTY L, CHOU TH, AL-KAITB A, KRAUT M, MARTINO S, CHEN B, KAPLAN J, VAIINVIESO M: A phase I trial of recombinant interleukin-2 combined with recombinant interferon-gamma in patients with cancer. J. Clin. Oncol. (1990) 8:1269–1276.
  • WEINER LM, PADAVIC-SHALLER K, KITSON J, WA1 Ls P, KRIGEL RE, LITWIN S: Phase I evaluation of combinant therapy with interleukin-2 and gamma-interferon. Can-cer Res. (1991) 51:3910–3918.
  • AGUET M, MOGENSEN ICE: Interferon receptors. In: In-terferon 3. Gresser I (Ed) New York Academic Press, 1983 p1–22,.
  • BROOKS CG, HOLSCHER M, URDAL D: Natural killer activity in cloned cytotoxic t lymphocytes: Regulation by interleukin-2, interferon, and specific antigen. J Immunol. (1985) 135:1145–1152.
  • BRUNDA MJ, ROSENBAUM D, STERN L: Inhibition of experimentally induced murine metastases by recom-binant alpha-interferon: on natural killer cell activity and inhibition of metastases. Intern. J. Cancer (1984) 24:421–426.
  • HERBERMANN RB, ORTALDO JR, MANTOVANI A, HOBBS DS, KUNG HF, PESTKA Sr Effect of human recombinant interferon on cytotoxic activity of natural killer cells and monocytes. Cell Immunol. (1982) 67:160–167.
  • LEE SH, Cl-RU H, RINDERKNECHT E, SABO W, STEBBING N: Importance of treatment regimen of interferon as an antitumor agent Cancer Res, (1983) 43:4172–4175.
  • KRIGEL RE, PADAVIC-SHALLER KA, RUDOLPH AR, LITWIN S, KONRAD M, BRADLEY EC, COMIS RE: A phase I study of recombinant interleukin- 2 plus recombinant p-in-terferon. Cancer Res. (1988) 48:3875–3881.
  • ZAMKOFF K, NEWMAN N, PAOLOZZI F, RUDOLPH A, BRADLEY E, DOYLE M, KONRAD M, ICIRSCHNER J, SZALZO A, DIFINO S, GULLO J, POIESZ B: A phase I study of recombinant interleukin-2 and recombinant 13-inter-feron in patients with advanced malignancy. Proc. Am, Assoc. Cancer Res. (1987) 6:242.
  • PAOLOZZI F, ZAMKOFF K, DOYLE M, KONRAD M, BRADLEY EC, RUDOLPH A, NEWMAN N, GULLO J, SZALO A, POIESZ B: Phase I trial of recombinant interleukin-2 and recombinant beta-interferon in refractory neoplas-tic diseases. J. Biol. Resp. Modifiers (1989) 8:122–139.
  • TAMURA T, SASAKI Y, SHINKAI T, EGUCHI K, SAKURAI M, FUJIWARA Y, NAKAGAWA K, MINATO K, BUNGO M, SAIJO N: Phase I study of combination therapy with inter-leukin-2 and 8-interferon in patients with advanced malignancy. Cancer Res. (1989) 49:730–735.
  • KRIGEL EL, PADAVIC-SHALLER KA, RUDOLPH AR, KON-RAD M, BRADLEY EC, COMIS RI: Renal cell carcinoma: Treatment with recombinant interleukin-2 plus 0-inter-feron. J. (En. Oncol. (1990) 8:460–467.
  • BORDEN EC: Augmented tumor-associated antigen ex-pression by interferon. J. Natl. Cancer Institute (1988) 80:8–14.
  • EDWARDS BS, HAWKINS MJ, BORDEN EC: Comparativein vivo and in vitro activation of human natural killer cells by two recombinant alpha-interferons differing in antiviral activity. Cancer Res. (1984) 44:3135–3139.
  • ISAACS A, LINDENMANN J: Virus interference. 1. The interferons. Proc. Royal Soc. Biol. Sciences 147:258.
  • KNOP J, TABORSKI B, DEMAEYER-GUIGNARD J: Selective Inhibition of the generation of T suppressor cells of contact sensitivity in vitro by interferon. J. Immunol. (1987) 138:3684–3687.
  • MURRAY JL, PILLOW JK, ROSENBLUM MG: Differential in vitro effects of recombinant alpha-interferon and re-combinant gamma- interferon on the expression of melanoma-associated antigens. Proc. Amer. Assoc. Cancer Res. (1986) 27:313.
  • QUESADA JR, RIOS A, SWANSON D: Antitumor activity of recombinant-derived interferon-alpha in metastatic re-nal cell carcinoma. J. Clin. Oncol. (1985) 3:1522–1528.
  • SUZUKI R, SUZUKI S, EBINA N, 1CUMAGAI K: Suppression of alloimmune cytotoxic T lymphocyte (CTL) genera-tion by depletion of NK cells and restoration by inter-feron and/or interleukin-2. J. Immunol. (1985) 134:2139–2148.
  • WAN YJ, ORRISON BM, LIEBERMAN R,: Induction of major histocompatibility class I antigens by interferons in undifferentiated F9 cells.j Cell Physiol. (1987) 130:76–283.
  • TALPAZ M, KANTARJIAN HM, MCCREEDIE K: Hematologicremission and cytogenic improvement induced by re-combinant human interferon- alpha 2A in chronic myelogenous leukemia. N. Engl. J. Med. (1986) 314:1065–1069.
  • CREAGAN ET, AHMANN DL, GREEN SJ: Phase II study of recombinant leukocyte alpha-interferon in dissemi-nated malignant melanoma. Cancer (1984) 54:2844–2849.
  • LEGHA SS: Interferons in the treatment of malignant melanoma. A review of recent trials. Cancer (1986) 57: 1675–1677.
  • KROWN SE: Interferon treatment of renal cell carci-noma: Current status and future prospectives. Cancer (1987) 59:647–651.
  • MUSS HB: Interferon therapy for renal cell carcinoma. Sem. Oncol. (1987) 15:36–42.
  • MANDELLI F, TRIBALTO M, AVVISATI G: Recombinant Interferon- alpha-2b as post-induction therapy for re- sponding multiple myeloma patients. Cancer Treatm. Rev. (1988) 15:43–48.
  • QUESADA JR, ALEXANIAN R, HAWKINS M, BARLOGIE B, BORDEN E, ITRI L, GUTTERMAN JU: Treatment of multi-ple myeloma with recombinant alpha-interferon. Blood (1986) 67:275–278.
  • ATZPODIEN J, SHIMAZAKI C, WISNIEWSKI D, GULATI S, BÜHRER CH, Oz S, LINK H, POLIWODA H, WELTE K, CLARKSON B: Interleukin-2 und interferon-alpha in der adoptoiven immuntherapie des plasmozytoms: ein ex-perimentelles Modell. In: Leukamien und Lymphotne. Lutz D, Heinz R, Nowotny H, Stacher A et al. (Eds) München, Wien, Baltimore, Urban & Schwarzenberg 1988, p211–212.
  • BRUNDA MJ, BELLANTONI D, SULICH V: in vivo antitumor activity of combinations of interferon-alpha and inter-leukin-2 in a murine modeL Correlation of efficiacy with the induction of cytotoxic cells resembling natural killer cells. Intern. J. Cancer (1987) 40:365–371.
  • CAMERON RB, MCINTOSH JK, ROSENBERG SA: Synergistic antitumor effects of combination immunotherapy with recombinant interleukin- 2 and a recombinant hybrid alpha-interferon in the treatment of established murine hepatic metastases. Cancer Res. (1988) 48:5810–5817.
  • SONE S, UTSUGI T, NH A, OGURA T: Differential effects of recombinant interferons alpha, beta, gamma on Induction of human lymphokine-activated killer activ-ity. J. Natl. Cancer Institute (1988) 80:425–431.
  • BASH JA, ARROYO PA, WLEGAND G, QUINTANA L, WAL-LACK MK: Direct effects of alpha-interferon on murine adenocarcinoma C-C 36 as a basis for synergy with interleukin-2 In cytolytic lymphocyte (CTL) mediated abrogiation of hepatic metastases. Proc. Amer. Assoc. Cancer Res. (1990) 31:251.
  • CHIKKALA NF, LEWIS I, ULCHAKER J, STANLEY J, TUBBS R, FINKE JH: Interactive effects of alpha-interferon a/d and interleukin-2 on murine lymphokine activated killer activity: Analysis at the effector and presursor level. Cancer Res. (1990) 50:1176–1182.
  • KIM B, WARNAKA P: Enhanced survival of alpha-inter-feron augmented interleukin-2 therapy of pulmonary metastases: Efficiacy comparable to interleukin-2 and lymphokine activated killer cells. J. Surg. Res. (1991) 50:40–46.
  • MCINTOSH JK, MULE JJ, KROCNICK JA, ROSENBERG SA: Combination cytokine immunotherapy with tumor ne-crosis factor alpha, interleukin-2 and its synergistic antitumor effects in mice. Cancer Res. (1989) 29:1408–1414.
  • TRUITT GA, STERN LL, BONTEMPO J: Recombinant hu-man interleukin-2, alone and in combination with Interferon-alpha, is a potent antitumor agent against colon 38 and Lewis lung carcinomas in mice. Proc. Amer. Assoc. Cancer Res. (1987) 28:369.
  • MUSS HB: Interferon therapy for renal cell carcinoma. Sem. Oncol. (1987) 15:36–42.
  • ATZPODIEN J, KIRCHNER H, LOPEZ-HANNINEN E, KOR-FER A, FENNER M, MENZEL T, DECKERT M, FRANZKE A,JONAS U, POLIWODA H: European studies of inter-leuldn-2 in metastatic renal cell carcinoma. Sem. Oncol. (1993) 20: 22–26.
  • SZNOL M, JANIK JE, SHARFMAN WH, STEIS RG, SMITH JW, URSA WJ, FENTON RG, CREEKMORE SP, FREY G, LONG DL: A phase la/lb study of subcutaneously administered interleukin-2 in combinantion with interferon-alpha 2a. Proc. Amer. Assoc. Clin. Oncol. (1991) 10:209.
  • FACENDOLA G, LABIANCA R, PIZZOCARO G, PIVA L, PEGORARO C, FAUSTINI M, LOMBARDI F, CLERICI M, SCANCI F, SIGNOROLDI A: Recombinant subcutaneous human interleukin-2 and alpha-2b-interferon in the treatment of advanced renal cell cancer Proc. Amer. Soc. Oncol.(1993) 13:762.
  • KIRCHNER H, LOPEZ-HÄNNINEN E, FENNER M, VOLKENANDT M, ATZPODIEN J: Chemoimmunotherapy of advanced malignant melanoma with carboplatin and DTIC followed by subcutaneous interleukin-2 and in-terferon-alpha. Proc. Amer. Soc. Clin. Oncol. (1993) 13:1356.
  • ATZPODIEN J, KIRCHNER H, SCHOMBURG A, ET AL.: Outpatient chetao-immunotherapy of advanced malig-nant melanoma:sequential administration of sc inter-leukin-2 and interferon-alpha after iv dacarbazine and carboplatin. Europ. J. Cancer (1994) In press.
  • HAMBLIN J, DAVIES B, SADULLAH S, OSICAM R, PALMER P, FRANKS CR: A phase II study of the treatment of metas-tatic malignant melanoma with a combination of dacar-bazine, cisplatin, interleukin-2 and alpha-interferon. Europ. J Cancer (1991) 27:123–127.
  • LEGHA SS, RING S, PLAGER C, PAPADOPOULOS N, GUT-TERMAN J, BENJAMIN RS: Biochemotherapy using inter-leukin-2 + interferon-alpha 2a in combination with cisplatin, vinblastine, and DTIC in advanced melanoma Proc. Amer. Soc. Clin. Oncol. (1991) 10:193.
  • RICHARDS JM: Sequential chemobrununotherapy for metastatic melanoma. Sem. Oncol. (1991) 18:91–95.
  • KHAYAT D, BOREL C, TOURANI JM, BENHAMMOUDA A, ANTOINE E, VUICLFMIN E, BAZEX PA, THILL L, FRANKS R,AUCLERC G, SOUBRANE C, BANZET P, WEIL M: Sequential chemoimmunotherapy with cisplatin, interleukin-2, and interferon alfa-2a for metastatic melanoma. J. Clin. Onc.(1993) 11:2173–2180.
  • ATZPODIEN J, KIRCHNER H, KORFER A, MENZEL T, SCHOMBURG A, POLIWODA H: Treatment of metastatic colorectal cancer patients with 5-fluorouracll in combi-nation with recombinant subcutaneous human inter-leukin-2 and interferon-alpha. Oncology In press.
  • HERSH EM, MURRAY JL, HONG WK, ROSENBLUM MG, REUBEN JM, WEILBAECHER R, SARWAL AN, BRADLEY EC, KONRAD M, ARNETT FC: Phase I study of cancer therapy with recombinant interleukin-2 adsninistered by intra-venous bolus injection. Biotherapy (1989) 1:215–226.
  • CHOU T, CHANG AE, SHU S: Generation of therapeutic T lymphocytes from tumor bearing mice by in vitro sensitization. J. Immunol. (1988) 140:2453–2461.
  • EDWARDS BS, HA'VVKINS MJ, BORDEN EC: Comparative in vivo and in vitro activation of human natural killer cells by two recombinant alpha-interferons differing in antiviral activity. Cancer Res. (1984) 44:3135–3139.
  • KIM B, FRANCESCHI D, HELMAN S, CLEVELAND RP, IM-BEMBO AL: Interferon inhibition of 11-2 mediated lym-phocyte proliferation. Surgery (1988) 104:390–397.
  • KURIBAYASILI K, GILLIS S, KERN DE, HENNEY CS: Murine NK cell cultures: Effects of interleukin-2 and interferon on cell growth .1. Immunol. (1981) 126:2321–2327.
  • KLEINERMANN ES, KURZROCK R, WYATT D, QUESADA JR, GUTTERMAN JU, FIDLER IJ: Action or suppression of the tumoticidal properties of monocytes from cancer pa-tients following treatment with human recombinant gamma-interferon. Cancer Res. (1986) 46:54001–5404.
  • SILAGI S, DUTKOWSKI R, SCHAEFER A: Eradication of mouse melanoma by combined treatment with recom-binant human interleukin- 2 and recombinant nturine Interferon-gamma. Intern au. J. Cancer (1988) 41:315–322.
  • BUDD GT, OSGOOD B, BARNA B, BOYETT JM, FINICE J, MEDENDORP SV, MURTHY S, NOVAK C, SERGI J, TUBBS R, BUKOWSKI RM: Phase I clinical trials of interleukin-2 and alpha-interferon: Toxicity and immunologic ef-fects. Cancer Res. (1989) 49:6432–6436.
  • AGAH R, MALLOY B, SHERROD A, MAZUMDER A: Success-ful therapy of natural killer resistant pulmonary metas-tases by the synergism of gamma-interferon with tumor necrosis factor and interleukin-2 in mice. Cancer Res. (1988) 48:2245–2248.
  • OWEN-SCHAUB LB, GUTTERMAN JU, GRIMM EA: Synergy of tumor necrosis factor and interleukin-2 in activation of human cytotoxk lymphocytes. Cancer Res. (1988) 48:788–792.
  • SLEIJER DT, JANSSEN RAJ, BUTER J, DE VRIES EGE, WILLEMSE PHB, MULDER NH: Phase II study of subcuta-neous interleukin-2 in unselected patients with ad-vanced renal cell carcinoma on an outpatient basis. J Clin. Oncol. (1992) 10:1119–1123,
  • FISHER RI, COLTMAN CA, DOROSHOW JH, PAIETTA EL: metastatic renal cancer treated with interleukin-2 and LAX cells. Ann. Inter. Med. (1988) 108:518–523.
  • MULE JJ, SMITH GRAIG A, ROSENBERG SA: Interleukin-4 can mediate the induction of lymphokin-activated kil-ler cell activity directed against fresh tumor cells. J. Exp. Med. (1987.) 166:792–797.
  • SPITS H, YSSEL H, TAKEBE Y, ARAI N, YOKOTA T, LEE F, ARAI RI, BANCHERAEU J, DEVRIES JE: Recombinant in-terleukin-4 promotes the growth of human T cells. J Immunol. (1987) 139:1142–1147.
  • JELINEK DF, LIPSKY PE: Inhibitory influence of 11-4 on human B cell responsiveness.J. Immunol. (1988)141:164–173.
  • DEFRANCE T, VANBERVLIET B, AUBRY J, BANCHEREAU J: Interleukin-4 inhibits the proliferation but not the differentiation of actvated human B cells in responce to interleukin-2. I Exp. Med. (1988) 168:1321–1333.
  • SPITS H, YSSEL H, PALIARD X, KASTELEIN R, FIGDOR C, DEVRLES JE: IL-4 inhibits 11-2 mediated induction of human lymphokine-activated killer cells, but not the generation of antigen-specific cytotoxic T lymphocytes In mixed leukocyte cultures. J. Immunol. (1988) 141:29–36.
  • KAWAKAMI Y, CUSTER MC, ROSENBERG SA, LOTZE MT: 11-4 regulates IL-2 induction of lymphokine-activated killer activity from human lymphocytes. J. Immunol. (1989) 142:452–3461.
  • HIGUCHI CM, THOMPSON JA, LINDGREN CG, GILLIS S, WIDMER MB, KERN DE, FEFER A: Induction of lymphok-ine-activated killer activity by interleukin-4 in human lymphocytes preactivated by interleukin 2 in vivo or in vitro. Cancer Res. (1989) 49:6487–6492.
  • BROOKS B, CHAPMAN K, LA.WRY J, MEAGER A, REES RC: Suppression of lymphokine-activated killer cell induc-tion mediated by interleukin-4 transforming growth factor 131: Effect of addition of exogenous tumor ne-crosisfactor-alpha and interferon-gamma, and meas-urement of their endogenous production. Clin. Exp. Immunol. (1990) 82:583–589.
  • FAVROT M, CAPDEVILLE R, COMBARET V, ZHOU DC, CLAPISSON G, BANCHEREAU j, FRANKS CR, CHOUAIB S, BLAY JY, PHILIP T: Functional and phenotypic modifi-cations induced by IL-4, as a single agent or in combi-nation with 11-2, on PBMC preactivated in vivo by alpha-interferon + interleukin-2 therapy. Eur. Cytokine Network (1990) 1:141–147.
  • MCBRIDE WH, ECONOMOU JS, NAYERSINA R, COMORA S, ESSNER R: Influence of interleukins 2 and 4 on tumor necrosis factor production by murine monocular phagocytes. Cancer Res. (1990) 50:2949–2957.
  • MARTINEZ OM, GIBBONS RS, GAROVOY MR, ARONSON FR: 11-4 inhibits 1L-2 receptor expression and IL-2-de-pendent proliferation of human T cells. J. Immunol. (1990) 144:2211–2215.
  • APRILE JA, RUSSO M, PEPE MS, LOUGHRAN TP: Activation signals leading to proliferation of normal and leukemic CD3+ large granular lymphocytes. Blood (1991) 78:1282–1285.
  • BOSSED, ADES E: Suppression of human immunoglobin synthesis by interleukin-4 in tandem with interleukin-2 through large granular lymphocytes. Pathobiology (1991) 59:391–395.
  • COX GW, CHATFOPADHYAY U, OPPENHEIM JJ, VARESIO L: 11–4 inhibits the costimulatory activity of 11.-2 or picolinic acid but not of lipopolysaccharide on 1FN-gamma treated macrophages. J. Immunol. (1991) 147:3809–3814.
  • PURI PK, LELAND P: In vivo treatment with interferon causes augmentation of IL-2 induced lymphokine-acti-vated killer cells in the organs of mice. Clin. Exp. Immunol. (1991) 85:317–325.
  • KAM JC, ET AL.: Combination IL-2 and 11–4 reduces glucocorticoid receptor-binding affinity and T cell re-sponse to glucocorticoids. J. Immunol. (1993) 151:3460–3466.
  • COLQUHOUN SD ET AL.: 11-4 inhibits 11-2 induction of LAK cytotoxicity in lymphocytes from a variety of lymphoid tissue. J. Surg. Res. (1993) 55:486–492.
  • CHOUAIB S, BERTOGLIO J, BLAY JY, MARCHIOL-FOURNI-GAULT C, FRADELIZI D: Generation of lymphokine-acti-vated killer cells: Synergy between tumor necrosis factor and interleukin-2. Immunology (1988) 85:6875–6879.
  • ESPEVIK T, FIGARI I, RANGES GE, PALLADINO MA: Trans-forming growth factor-131 and recombinant human tumor necrosis factor-alpha reciprocally regulate the generation of lymphokine-activatefikiller cell activity. J. Immunol. (1988) 140:2312–2316.
  • OWEN-SCHAUB LB, GUTTERMAN JU, GRIMM EA: Synergy of tumor necrosis factor and interleukin 2 in the acti-vation of human cytotoxic lymphocytes: Effect of tumor necrosis factor and interleukin 2 in the generation of human iymphokine-activated killer cell cytotoxicity. Cancer Res. (1988) 48:788–792.
  • BLAY JY, BERTOGLIO J, FRADELIZI D, CHOUAIB S: Func-tional interaction of IL-2 and TNF in the differentiation of LGL into LAK effectors. Intern.J. Cancer (1989) 44:598–604.
  • YANG SC, OWEN-SCHAUB LB, GRIMM EA, ROTH JA: In-duction of lymphokine-activated killer cytotoxicity with interleukin-2 and tumor necrosis factor-alpha against primary lung cancer targets. Cancer. Immunol. Immunoth. (1989) 29:193–108.
  • FAVROT M, COMBARET V, BLAY JY, CAPDEVILLE R, ZHOU DC, CLAPISSON G, CHOUAIB S, FRANKS CR, PHILLIP T: INF-alpha enhancement of NK and LAK cell functions Induced by high-dose 11-2 in human peripheral blood mononuclear cells from patients pretreated with alpha-IFN + IL-2. Eur. Cytokine Network (1990) 1:221–227.
  • MOXEY-MIMS MM, SIMMS H, FRANK MM, UN EY, GAITHER TA: The effects of 1L-1, 11-2, and tumor necrosis factor on polymorphonuclear leukocytes Fe gamma receptor-mediated phagocytisis:IL-2 downregulates the effect of tumor necrosis factor. J. Immunol. (1991) 147:1823–1830.
  • LAUZON W, LEMAIRE I: Effects of biological response modifiers of lung natural killer activity. Immunophar-macol. Immunotaxicol. (1991) 13:237–250.
  • DANIS VA, FRANIC GM, RATHJEN DA, BROOKS PM: Effects of granulocyte-macrophage colony-stimulating factor (GM-CSF), 11-2, interferon-gamma, tumor necrosis fac-tor-alpha and 11-6 on the production of inununoreac-tive IL-1 and TNF- alpha by human monocytes. Clin. Exp. Immunol. (1991) 85:143–450.
  • NISHIMURA T, OHTA S, SATO N, TOGASHI Y, GOTO M, HAHIMOTO Y: Combination tumor-immunotherapy with recombinant tumor necrosis factor and recombi-nant interleukin 2 in mice. Intern. J. Cancer (1987) 40:255–261.
  • WINKELHAICE JI, STAMPFL S, ZIMMERMAN RJ: Synergistic effects of combination therapy with human recombi-nant interleukin-2 and tumor necrosis factor-alpha against primary lung cancer targets. Cancer Immunol. Immunoth. (1989) 29:193–108.
  • MCINTOSH JK, MULE JJ, MERINO MJ, ROSENBERG SA: Synergistic antitumor effects of immunotherapy with recombinant tumor necrosis factor-alpha. Cancer Res. (1988) 48:4011–4017.
  • PURI RK, TRAVIS WD, ROSENBERG SA: In vivo admini-stration of interferon-alpha and interleukin-2 induces proliferation of lymphoid cells in the organs of mice. Clin. Exp. Immunol. (1991) 85:317–325.
  • URANO K, ET AL.: Potentiation of therapeutic effect of recombinant tumor necrosis factor against B16 mouse melanoma by combination with 11–2. Cytokine (1993) 5:224–229.
  • SVEDERSKY LP, SHEPARD HM, SPENCER SA, SHALABY MR, PALLADINO MA: Augmentation of human natural cell-mediated cytotoxicity by recombinant human inter-leukin-2. J. Immunol. (1984) 133:714–718.
  • NEDWIN GE, SVEDERSKY LP, BRINGMAN TS, PALLADINO MA, GOEDDEL DV:Effect of interleukin-2, interferon -gamma, and mitogens on the production of tumor necrosis factor alpha and beta. J. Immunol. (1985) 135:2492–2497.
  • SVEDERSKY LP, NEDWIN GE, GOEDDEL DV, PALLADINO MA: Interferon-gamma enhances induction of lympho- toxin in recombinant interleukin-2 stimulated periph-eral blood mononuclear cells. J. Immunol. (1985) 134:1604–1608.
  • BRAAKMAN E, VAN TUNEN A, MEAGER A, LUCAS CJ: IL-2 and ifn-gamma enhanced natural cytotoxic activity: analysis of the role of different lymphoid subsets and Implications for activation routes. Cellular Immunol. (1986) 99:476–488.
  • BRUNDA MJ, TARNOWSKI D, DAVATELIS V: Interaction of recombinant interferons with recombinant inter-leukin-2: differential effects on natural killer cell activ-ity and interleuldn-2-activated killer cells. Internatl. J. Cancer (1986) 37:787–793.
  • DAUGHERTY JP, WEINER LM: Augmentation of IL-2 in-duced IL-2 receptor expression by IFN-gamma. Proc. Amer. Assoc. Cancer Res. (1987) 28:341–344.
  • HERRMANN F, GEBAUER G, LINDEMANN A, BRACH M, MERTELSMANN RH: Interleukin-2 and interferon-gamma recruit different subsets of human peripheral blood monocytes to secrete interleukin-1 and tumor necrosis factor-alpha. Clin. Exp. Immunol. (1989) 77:97.
  • TOLEDANO M, MATHIOT C, MICHON J, ANDREU G, LANDO D, BRANDELY M, FRIDMAN WH: Interferon-gamma and interleukin-2 in the generation of lymphok-ine-activated killer cell cytotoxicity. Cancer Immunol. Immunotb. (1989) 30:57–62.
  • NARUMI S. FINKLE JH, HAMILTON TA: Interferon-gamma and interleukin-2 synergize to induce selective monok-ine expression in murine pertoneal macrophages. J. Biol. Chem. (1990) 265:7036–7041.
  • BELOSEVIC M, FINBLOOM DS, MELTZER MS, NACY CA: IL-2. A cofactor for induction of activated macrophage resistance to infection. J. Immunol. (1990) 145:831–836.
  • COX GW, MATHIESON BJ, GIARDINA SL, VARESIO L: Characterization of IL-2 receptor expression and func-tion on murine macrophages. J. Immunol. (1990) 145:1719–1725.
  • KAUFMANN J, DAVIDSOHN J, LEVANON M, ICEKSON I, REVEL M, RAMOT B: Lymphokine-activated killer cells: Interferon-gamma synergizes with interleukin-2 to in-duce LAK cytotoxicity in homogeneous leukemic preparations. Clin. Immunol. Immunopathol. (1991) 58:278–288.
  • GUSELLA GL, ET AL.: I1-2 up-regulates but IFN-gamma suppresses 11–8 expression inhuman monocytes. j Im-munol. (1993) 151:2725–2732.
  • MCADAM, ET AL.: Coexpression of interleukin-2 and gamma-interferon enhances tumor immunity. Ann. NY Acad. Sci. (1993) 690:349–351.
  • DUBINETT SM, KURNICK JT, KRADIN RE: Analysis of the local inflammatory response to adoptive immuno-therapy with activated lymphocytes, LEN-gamma, and IL-2. FASEB J. (1988) 2:2286.
  • IIGO M, SAKURAI M, TAMURA T, NAGAHIRO S, HOSHI A: In vivo antitumor activity of multiple infections of recombinant interleukin-2, alone and in combination with three different types of recombinant interferon, on various syngeneic murine tumors. Cancer Res. (1988) 48:260–264.
  • VAAGE J: Peel-tumor interleukin-2 causes systemic therapeutic effect via interferon-gamma induction. In-ternatl. J. Cancer (1991) 49:598–600.
  • KURLBAYASHI K, GILLIS S, KERN DE, HENNEY CS: Murine NK cell cultures: Effects of interleukin-2 and interferon on cell growth and cytotoxic reactivity. J. Immunol. (1981) 126:2321–2327.
  • BROOKS CG, HOLSCHER M, URDAL D: Natural killer activity in cloned cytotoxic T Lymphocytes. Regulation by interleukin-2, interferon, and specific antigen. J. Immunol. (1985) 135:1145–1152.
  • VANDEGRIEND RJ, RONTELTAP CPM, GRAVEKAMP C, MONNIKENDAMM D, BOLHUIS RLH:and recombi-nant interleukin-2 can both enhance, but by different pathways, the nonspecific cytolytic potential of T3-negative natural killer cell-derived clones rather thean that of T3-positive clones. J. Immunol. (1986) 136:1700–1707.
  • KORNBLUTH J, HOOVER RG: Changes in gene expres-sion associated with IFN-13 and IL-2 induced augmenta-tion of human natural killer cell function_ J. Immunol. (1988) 141:3234–3240.
  • LAUZON W, LEMAIRE I: Effect of biological response modifiers on lung natural killer activity. Immunophar-macol. Immunotaxicol. (1991) 13:237–250,
  • IIGO M, SAKURAI M, SHIMIZU M, IIZUICA T, SA1J0 N, HOSHI A: Synergistic inhibition of the growth of adeno-carcinoma 755 by the combination of interleultin-2 and Interferon-D. Proc.Japanese Acad. Soc. (1986) 62:275–278.
  • HENNEY CS, KURIBAYASHI K, KERN DE, GILDS S; Inter-leukin-2 augments natural killer cell activity. Nature (1981) 291:335–338.
  • DIRAIMONDO F, LAPUSHIN R, HERSH EM: Synergism between alpha-interferon and interleukin-2 activated killer cells: in vitro studies. Acta Haematologica (1987) 78:77–83.
  • TOKUDA Y, EBINA N, GOLUB SH: The inhibitory effect of human interferon alpha on the generation of lym-phokine-activated killer activity. Cancer Immunology and Immunotherapy (1989) 30:205–212.
  • BERGMANN L, WEIDMANN E, BUNGERT B, HECHLER P, MITOU PS: Influence of various cytokines on the induc-tion of lymphokine-activated killer cells. Natl. Immunol. Cell. Growth Regulatory (1990) 9:265–273.
  • LAUZON W, LEMAIRE I : Effect of biological response modifiers on lung natural killer activity. Immunopbar-macol. Immunotoxicol. (1991.) 13:237–250.
  • KIM B, STEIN 5, WARNAKA P, FRANCESCHI D: Enhanced in vivo therapy of pulmonary metastases with inter-feron and interleukin. j Surg. Res. (1988) 45:66–73.
  • PURI MC, TRAVIS WD, ROSENBERG SA: In vivo admini-stration of interferon alpha and interleukin-2 induces proliferation of lymphoid cells in the organs of mice. Cancer Res. (1990) 50:5543–5550.
  • SCHENDEL DJ, ET AL.: Tumor-specific lysis of human renal cell carcinomas by tumor-infiltrating lympho-cytes:modulation of recognition through retroviral transduction of tumor cells with interleukin-2 comple-mentary DNA and exogeneous alpha interferon treat-ment. Cancer Res. (1993) 53:4020–4025.
  • West WH: Clinical application of continuous infusion of recombinant interleukin-2. Eur. J. Cancer Clin. Oncol. (1989) 25:11–15.
  • OLENCKI T, NATAJI B, BUDD GT, FINKE J, MURTHY S, HERZOG P, TUBBS R, THOMASSEN MJ, BAUER L, SERGI JS, BUKOWSKI RM: Phase 1 trial of rIL-2 and rhulL-4 in patients with refractory malignancy: Hematologic and Immunologic effects. Blood (1991) 78:439a.
  • KRUIT WHJ, GOEY SH, MONSON JRT, STAHEL RA, CALABRESI F, MERTELSMANN R, HOLDNEREE, EGGER-MONT AMM, BOLDHIUS RLH, DEMULDER PHM, STOTER G: Clinical experience with the combined use of recom-binant interleukin-2 and interferon alpha 2a in metas-tatic melanoma. Br. J. Haematol. (1991) 79:84–86.
  • SPARANO JA, MICETICH KC, SUNDERLAND M, MARGOLIN K, ARONSON F, SZNOL M, RUBINSTEIN LV: A randomized phase M trial of treatment with high-dose interleulcin-2 either alone or in combination with interferon-2 alpha In patients with advanced melanoma. Proc. Amer. Soc. Oncol. (1993) 12:1332.
  • LEE ICH, TALPAZ M, ROTHBERG JM, MURRAY JL, PA-PADOPOULOS N, PLAGER C, BENJAMIN R, LEVTIT D, GUTTERMANN J: Concomittant administration of re-combinant human interleukin-2 and recombinant in-terferon alpha-2a in cancer patients: A phase I study. J. Oncol. (1989.) 7:1726–1732.
  • BERGMANN L, WEIDMANN E, MITROTJ PS, RUNNE U, KEILHOLZ U, BARTSCH HI-I, FRANKS CR: Interleukin-2 in combination with interferon-alpha in dissetnenated malignant melanoma and advanced renal cell carci-noma. Onkologie (1990) 13:137–140.
  • BUKOWSKI RM, MURTHY S, SERGI J, BUDD GT, MCKEEVER S, MEDENDORP SV, ZUBBS-GIBSON V, FINKE J: Phase I trial of continuous infusion recombinant interleukin-2 and intermittent recombinant interferon alpha 2a. J. Biol. Modifiers (1990) 9:538–545.
  • HIRSH M, LIPTON A, HARVEY H, GIVA1NT E, HOPPER K, JONES G, ZEFFREN J, LEVITT D: Phase I study of inter-leukin-2 and interferon alpha-2a as outpatient therapy for patients with advanced malignancy. J. Ctn. Oncol. (1990) 8:1657–1663.
  • HUBERMAN M, BERING H, FALLON B, TESSITORE J, SON-NENBORN H, PAUL S, ZEFFREN J, LEVITT D, GROOPMAN J: A phase I study of an outpatient regimen of recombi-nant human interleukin-2 and alpha-interferon in pa-tients with solid tumors. Cancer (1991) 68: 1708-1713.
  • KEILHOLZ U, SCHEIBENBOGEN C, TILGEN W, BERGMANN L, BRADO B, RICHTER M, SEITHER E, HUNSTEIN W: Treat-ment of metastatic melanoma with interferon-alpha and interleukin-2: Significant improvement with a new dosing schedule. Onkologie (1991) 14:82.
  • PICHERT G, JOST LM, FIERZ W, STAHEL RA: Clinical and Immune modulatory effects of alternative weekly inter-leulcin-2 and interferon-alpha-2a in patients with ad-vanced renal cell carcinoma and melanom. Br.J. Cancer (1991 ) 63:287–292.
  • LOPEZ M, CARPANO S, CANCRINI A, MAECELLINI M, DEL-MEDICO M, RINALDI M, V1CI P: IL-2 by continuous intra-venous infusion in advanced renal cell carcinoma. Proc. Am. Soc. Clin. Oncol. (1993) 12:792.
  • HAYAKAWA K, FUKUSHIMA T, SEITO D, ASAICURA Y, YAMANAKA Y, mourA T, SASAKI M, KONN M, ONO K: Continuous arterial infusion therapy of recombinant interleukin-2 and cylophosphamide in liver metastasis. Gan to Kagaku Ryobo (1989) 16:2842–2844.
  • ISRAEL L, BOAZIZ C, MOLIARD M, MORERE JF, BREAU JL: Phase 11 study of interleukin-2 in 18 patients with advanced gastrointestinal tract cancers. Proc. ASCO (1991) 10:147.
  • STEIS RG, URSA WJ, VANDERMOLEN LA, E7'AL.: Intraperi-toneal lymphokine-activated killer cell and interleukin-2 therapy for malignancies limited to the peritoneal cavity. J. Clin. Oncol. (1990) 8:1618–1629.
  • H1DDEMANN W, RUELFS C, 01 I hNSMEIER C, RUCKLE H, MUSCH E, KOCH O VAN DE LOO J: Interleukin-2 fol-lowed by S-fluorouracil and folinic acid in refractory colorectal cancer- results of a phase II study. Semin. Oncol. (1992) 19:225–227.
  • ARINAGA S, KARIMINE N, TAICAMUKA K, NANBARA S, AKIYOSHI T: Enhanced induction of LA.K activity after lentinasi administration in patients with gastric carci-noma. Int.J. Immunopbarmacol. (1992) 14:535–539,
  • TALEGHANI BM, POROWSKI P, KLINK M, GUNZER Uln-terleukin-2 and alpha-interferon sc in combination with 5-fluorouracil and folinic acid iv in advanced progressive colorectal cancer. Ann. Hematol. (1991) 6:126.
  • ZIEGLER LD, PALAZZOLO P, CUNNINGHAM J, JANUS M, TTOH K, HAYAKAWA K, MURRAY JL: Phase I trial of murine monoclonal antibody L6 in combination with subcutaneous interleukin-2 in patients with advanced carcinoma of breast, colorectal, and lung. J. Gun. Oncol. (1992) 10:1470–1478.

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