Abstract
Twenty-five years ago, we reported the production of the monoclonal antibody, anti-Tac that identifies the IL-2 receptor alpha subunit and blocks the interaction of IL-2 with this growth factor receptor. In 1997, daclizumab (Zenapax®), the humanized form of this antibody, was approved by the FDA for use in the prevention of renal allograft rejection. In addition, we demonstrated that daclizumab is of value in the treatment of patients with noninfectious uveitis, multiple sclerosis, and the neurological disease human T-cell lymphotropic virus I associated myelopathy/tropical spastic paraparesis (HAM/TSP). Others demonstrated therapeutic efficacy with daclizumab in patients with pure red cell aplasia, aplastic anemia, and psoriasis. Thus, translation of basic insights concerning the IL-2/IL-2 receptor system obtained using the monoclonal antibody daclizumab provided a useful strategy for the prevention of organ allograft rejection and the treatment of patients with select autoimmune diseases or T-cell leukemia/lymphoma.




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Uchiyama T, Broder S, Waldmann TA: 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, 1981
Uchiyama T, Nelson DL, Fleisher TA, Waldmann TA: A monoclonal antibody (anti-Tac) reactive with activated and functionally mature human T-cells II expression of Tac antigen on activated cytotoxic killer T-cells suppressor cells and on one of two types of helper T-cells. J Immunol 126:1398–1403, 1981
Wiseman LR, Faulds D: Daclizumab: A review of its use in the prevention of acute rejection in renal transplant recipients. Drugs 58:1029–1042, 1999
Waldmann TA: The multi-subunit interleukin-2 receptor. Annu Rev Biochem 58:875–911, 1989
Waldmann TA: The IL-2/IL-2 receptor system: A target for rational immune intervention. Immunol Today 14:264–270, 1993
Foss FM, Waldmann TA: Interleukin-2 receptor-directed therapies for cutaneous lymphomas. Hematol Oncol Clin N Am 17:1449–1458, 2003
Waldmann TA, Goldman CK, Bongiovanni KF, Sharrow SO, Davey MP, Cease KB, Greenberg SJ, Longo DL: Therapy of patients with human T-cell lymphotrophic virus I-induced adult T-cell leukemia with anti-Tac a monoclonal antibody to the receptor for interleukin-2. Blood 72:1805–1816, 1988
Waldmann TA, White JD, Carrasquillo JA, Reynolds JC, Paik CH, Gansow OA, Brechbiel MW, Jaffe ES, Fleisher TA, Goldman CK, Top LE, Bamford R, Zaknoen E, Roessler E, Kasten-Sportes C, England R, Litou H, Johnson JA, Jackson-White T, Manns A, Hanchard B, Junghans RP, Nelson DL: Radioimmunotherapy of interleukin-2R alpha-expressing adult T-cell leukemia with Yttrium-90-labeled anti-Tac. Blood 86:4063–4075, 1995
Morris JC, Waldmann TA: Advances in interleukin 2 receptor targeted treatment. Ann Rheum Dis 59(Suppl 1):i109–i114, 2000
Vincenti F, Kirkman R, Light S, Bumgardner G, Pescovitz M, Halloran P, Neylan J, Wilkinson A, Ekberg H, Gaston R, Backman L, Burdick J: Interleukin-2-receptor blockade with daclizumab to prevent acute rejection in renal transplantation Daclizumab triple therapy study group. N Engl J Med 338:161–165, 1998
Waldmann TA, O’Shea J: The use of antibodies against the IL-2 receptor in transplantation. Curr Opin Immunol 10:507–512, 1998
Nussenblatt RB, Fortin E, Schiffman R, Rizzo L, Smith J, Van VP, Sran P, Yaffe A, Goldman CK, Waldmann TA, Whitcup SM: Treatment of noninfectious intermediate and posterior uveitis with the humanized anti-Tac mAb: A phase I/II clinical trial. Proc Natl Acad Sci USA 96:7462–7466, 1999
Nussenblatt RB, Thompson DJ, Li Z, Chan CC, Peterson JS, Robinson RR, Shames RS, Nagarajan S, Tang MT, Mailman M, Velez G, Roy C, Levy-Clarke GA, Suhler EB, Djalilian A, Sen HN, Al-Khatib S, Ursea R, Srivastava S, Bamji A, Mellow S, Sran P, Waldmann TA, Buggage RR: Humanized anti-interleukin-2 (IL-2) receptor alpha therapy: Long-term results in uveitis patients and preliminary safety and activity data for establishing parameters for subcutaneous administration. J Autoimmun 21:283–293, 2003
Bielekova B, Richert N, Howard T, Blevins G, Markovic-Plese S, McCartin J, Frank JA, Wurfel J, Ohayon J, Waldmann TA, McFarland HF, Martin R: Humanized anti-CD25 (daclizumab) inhibits disease activity in multiple sclerosis patients failing to respond to interferon beta. Proc Natl Acad Sci USA 101:8705–8708, 2004
Lehky TJ, Levin MC, Kubota R, Bamford RN, Flerlage AN, Soldan SS, Leist TP, Xavier A, White JD, Brown M, Fleisher TA, Top LE, Light S, McFarland HF, Waldmann TA, Jacobson S: Reduction in HTLV-I proviral load and spontaneous lymphoproliferation in HTLV-I-associated myelopathy/tropical spastic paraparesis patients treated with humanized anti-Tac. Ann Neurol 44:942–947, 1998
O’Mahony D, Morris JC, Carrasquillo JA, Le N, Paik CH, Whatley M, Pittaluga S, Fleisher TA, Lee C, Gao W, O’Hagan D, Brechbiel M, Waldmann TA, Janik JE: Phase I/II study of Yttrium-90 labeled humanized anti-Tac (HAT) monoclonal antibody and calcium DTPA in CD25-expressing malignanices. J Nucl Med 47:98P, 2006
Köhler G, Milstein C: Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256:495–497, 1975
Ehrlich P: On immunity with special reference to cell life: Croonian lecture. In The Collected Papers of Paul Ehrlich, B Himmelweir (ed). London, Pergammon, 1956, pp 148–192
Schwartz RH: T-lymphocyte recognition of antigen in association with gene products of the major histocompatibility complex. Annu Rev Immunol 3:237–261, 1985
Robb RJ, Munck A, Smith KA: T-cell growth factor receptors quantitation specificity and biological relevance. J Exp Med 154:1455–1474, 1981
Waldmann TA: The meandering 45-year odyssey of a clinical immunologist. Annu Rev Immunol 21:1–27, 2003
Leonard WJ, Depper JM, Uchiyama T, Smith KA, Waldmann TA, Greene WC: A monoclonal antibody that appears to recognize the receptor for human T-cell growth factor; partial characterization of the receptor. Nature 300:267–269, 1982
Leonard WJ, Depper JM, Kronke M, Robb RJ, Waldmann TA, Greene WC: The human receptor for T-cell growth factor evidence for variable post-translational processing phosphorylation sulfation and the ability of precursor forms of the receptor to bind T-cell growth factor. J Biol Chem 260:1872–1880, 1985
Leonard WJ, Depper JM, Crabtree GR, Rudikoff S, Pumphrey J, Robb RJ, Kronke M, Svetlik PB, Peffer NJ, Waldmann TA, Greene WC: Molecular cloning and expression of cDNAs for the human interleukin-2 receptor. Nature 311:626–631, 1984
Leonard WJ, Depper JM, Kanehisa M, Kronke M, Peffer NJ, Svetlik PB, Sullivan M, Greene WC: Structure of the human interleukin-2 receptor gene. Science 230:633–639, 1985
Tsudo M, Kozak RW, Goldman CK, Waldmann TA: Demonstration of a non-Tac peptide that binds interleukin 2: a potential participant in a multichain interleukin 2 receptor complex. Proc Natl Acad Sci USA 83:9694–9698, 1986
Sharon M, Klausner RD, Cullen BR, Chizzonite R, Leonard WJ: Novel interleukin-2 receptor subunit detected by cross-linking under high-affinity conditions. Science 234:859–863, 1986
Sugamura K, Asao H, Kondo M, Tanaka N, Ishii N, Ohbo K, Nakamura M, Takeshita T: The interleukin-2 receptor gamma chain: Its role in the multiple cytokine receptor complexes and T-cell development in XSCID. Annu Rev Immunol 14:179–205, 1996
Noguchi M, Nakamura Y, Russell SM, Ziegler SF, Tsang M, Cao X, Leonard WJ: Interleukin-2 receptor gamma chain: A functional component of the interleukin-7 receptor. Science 262:1877–1880, 1993
Sakaguchi S: Naturally arising CD4+ regulatory T-cells for immunologic self-tolerance and negative control of immune responses. Annu Rev.Immunol 22:531–562, 2004
Cooper MA, Fehniger TA, Turner SC, Chen KS, Ghaheri BA, Ghayur T, Carson WE, Caligiuri MA: Human natural killer cells: A unique innate immunoregulatory role for the CD56(bright) subset. Blood 97:3146–3151, 2001
Depper JM, Leonard WJ, Robb RJ, Waldmann TA, Greene WC: Blockade of the interleukin-2 receptor by anti-Tac antibody: Inhibition of human lymphocyte activation. J Immunol 131:690–696, 1983
Korsmeyer SJ, Greene WC, Cossman J, Hsu SM, Jensen JP, Neckers LM, Marshall SL, Bakhshi A, Depper JM, Leonard WJ, Jaffe ES, Waldmann TA: Rearrangement and expression of immunoglobulin genes and expression of Tac antigen in hairy cell leukemia. Proc Natl Acad Sci USA 80:4522–4526, 1983
Holter W, Goldman CK, Casabo L, Nelson DL, Greene WC, Waldmann TA: Expression of functional IL 2 receptors by lipopolysaccharide and interferon-gamma stimulated human monocytes. J Immunol 138:2917–2922, 1987
Herrmann F, Cannistra SA, Levine H, Griffin JD: Expression of interleukin 2 receptors and binding of interleukin 2 by gamma interferon-induced human leukemic and normal monocytic cells. J Exp Med 162:1111–1116, 1985
Waldmann TA: The structure function and expression of interleukin-2 receptors on normal and malignant lymphocytes. Science 232:727–732, 1986
Depper JM, Leonard WJ, Kronke M, Noguchi PD, Cunningham RE, Waldmann TA, Greene WC: Regulation of interleukin 2 receptor expression: Effects of phorbol diester phospholipase C and reexposure to lectin or antigen. J Immunol 133:3054–3061, 1984
Reem GH, Yeh NH: Interleukin 2 regulates expression of its receptor and synthesis of gamma interferon by human T lymphocytes. Science 225:429–430, 1984
Cantrell DA, Smith KA: Transient expression of interleukin 2 receptors Consequences for T-cell growth. J Exp Med 158:1895–1911, 1983
Rubin LA, Nelson DL: The soluble interleukin-2 receptor: Biology function and clinical application. Ann Intern Med 113:619–627, 1990
Waldmann TA, Goldman CK, Robb RJ, Depper JM, Leonard WJ, Sharrow SO, Bongiovanni KF, Korsmeyer SJ, Greene WC: Expression of interleukin 2 receptors on activated human B cells. J Exp Med 160:1450–1466, 1984
Schorle H, Holtschke T, Hunig T, Schimpl A, Horak I: Development and function of T-cells in mice rendered interleukin-2 deficient by gene targeting. Nature 352:621–624, 1991
Sadlack B, Kuhn R, Schorle H, Rajewsky K, Muller W, Horak I: Development and proliferation of lymphocytes in mice deficient for both interleukins-2 and -4. Eur J Immunol 24:281–284, 1994
Waldmann TA, Dubois S, Tagaya Y: Contrasting roles of IL-2 and IL-15 in the life and death of lymphocytes: implications for immunotherapy. Immunity 14:105–110, 2001
Zhang X, Sun S, Hwang I, Tough DF, Sprent J: Potent and selective stimulation of memory-phenotype CD8+ T-cells in vivo by IL-15. Immunity 8:591–599, 1998
Ku CC, Murakami M, Sakamoto A, Kappler J, Marrack P: Control of homeostasis of CD8+ memory T-cells by opposing cytokines. Science 288:675–678, 2000
Marks-Konczalik J, Dubois S, Losi JM, Sabzevari H, Yamada N, Feigenbaum L, Waldmann TA, Tagaya Y: IL-2-induced activation-induced cell death is inhibited in IL-15 transgenic mice. Proc Natl Acad Sci USA 97:11445–11450, 2000
Waldmann TA: The biology of interleukin-2 and interleukin-15: Implications for cancer therapy and vaccine design. Nat Rev Immunol 6:595–601, 2006
Sakaguchi S: Naturally arising CD4+ regulatory T-cells for immunologic self-tolerance and negative control of immune responses. Annu Rev Immunol 22:531–562, 2004
Lenardo MJ: Fas and the art of lymphocyte maintenance. J Exp Med 183:721–724, 1996
Roifman CM: Human IL-2 receptor alpha chain deficiency. Pediatr Res 48(1):6–11, 2000
Lodolce JP, Boone DL, Chai S, Swain RE, Dassopoulos T, Trettin S, Ma A: IL-15 receptor maintains lymphoid homeostasis by supporting lymphocyte homing and proliferation. Immunity 9:669–676, 1998
Kennedy MK, Glaccum M, Brown SN, Butz EA, Viney JL, Embers M, Matsuki N, Charrier K, Sedger L, Willis CR, Brasel K, Morrissey PJ, Stocking K, Schuh JC, Joyce S, Peschon JJ: Reversible defects in natural killer and memory CD8 T-cell lineages in interleukin 15-deficient mice. J Exp Med 191:771–780, 2000
Kirkman RL, Shapiro ME, Carpenter CB, Milford EL, Ramos EL, Tilney NL, Waldmann TA, Zimmerman CE, Strom TB: Early experience with anti-Tac in clinical renal transplantation. Transplant Proc 21:1766–1768, 1989
Tinubu SA, Hakimi J, Kondas JA, Bailon P, Familletti PC, Spence C, Crittenden MD, Parenteau GL, Dirbas FM, Tsudo M, Bacher JD, Kastensprtes C, Waviucci JL, Gddman CK Clark Re Waldman TA: Humanized antibody directed to the IL-2 receptor beta-chain prolongs primate cardiac allograft survival. J Immunol 153:4330–4338, 1994
Uchiyama T, Yodoi J, Sagawa K, Takatsuki K, Uchino H: Adult T-cell leukemia: Clinical and hematologic features of 16 cases. Blood 50:481–492, 1977
Shimoyama M: Diagnostic criteria and classification of clinical subtypes of adult T-cell leukaemia-lymphoma A report from the Lymphoma study group (1984–87). Br J Haematol 79:428–437, 1991
Jeang KT: Functional activities of the human T-cell leukemia virus type I Tax oncoprotein: cellular signaling through NF-kappa B. Cytokine Growth Factor Rev 12:207–217, 2001
Uchiyama T: Human T-cell leukemia virus type I (HTLV-I) and human diseases. Annu Rev Immunol 15:15–37, 1997
Kirkman RL, Shapiro ME, Carpenter CB, McKay DB, Milford EL, Ramos EL, Tilney NL, Waldmann TA, Zimmerman CE, Strom TB: A randomized prospective trial of anti-Tac monoclonal antibody in human renal transplantation. Transplant Proc 23:1066–1067, 1991
Queen C, Schneider WP, Selick HE, Payne PW, Landolfi NF, Duncan JF, Avdalovic NM, Levitt M, Junghans RP, Waldmann TA: A humanized antibody that binds to the interleukin 2 receptor. Proc Natl Acad Sci USA 86:10029–10033, 1989
Junghans RP, Waldmann TA, Landolfi NF, Avdalovic NM, Schneider WP, Queen C: Anti-Tac-H a humanized antibody to the interleukin 2 receptor with new features for immunotherapy in malignant and immune disorders. Cancer Res 50:1495–1502, 1990
Jones PT, Dear PH, Foote J, Neuberger MS, Winter G: Replacing the complementarity-determining regions in a human antibody with those from a mouse. Nature 321:522–525, 1986
Nashan B, Light S, Hardie IR, Lin A, Johnson JR: Reduction of acute renal allograft rejection by daclizumab. Daclizumab Double Therapy Study Group. Transplantation 67:110–115, 1999
Carswell CI, Plosker GL, Wagstaff AJ: Daclizumab: A review of its use in the management of organ transplantation. BioDrugs 15:745–773, 2001
Beniaminovitz A, Itescu S, Lietz K, Donovan M, Burke EM, Groff BD, Edwards N, Mancini DM: Prevention of rejection in cardiac transplantation by blockade of the interleukin-2 receptor with a monoclonal antibody. N Engl J Med 342:613–619, 2000
Kobashigawa J, David K, Morris J, Chu AH, Steffen BJ, Gotz VP, Gordon RD: Daclizumab is associated with decreased rejection and no increased mortality in cardiac transplant patients receiving MMF cyclosporine and corticosteroids. Transplant Proc 37:1333–1339, 2005
Eckhoff DE, McGuire B, Sellers M, Contreras J, Frenette L, Young C, Hudson S, Bynon JS: The safety and efficacy of a two-dose daclizumab (Zenapax) induction therapy in liver transplant recipients. Transplantation 69:1867–1872, 2000
Niemeyer G, Koch M, Light S, Kuse ER, Nashan B: Long-term safety tolerability and efficacy of daclizumab (Zenapax) in a two-dose regimen in liver transplant recipients. Am J Transplant 2:454–460, 2002
Shapiro AM, Lakey JR, Ryan EA, Korbutt GS, Toth E, Warnock GL, Kneteman NM, Rajotte RV: Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med 343:230–238, 2000
Phillips KE, Herring B, Wilson LA, Rickford MS, Zhang M, Goldman CK, Tso JY, Waldmann TA: IL-2R alpha directed monoclonal antibodies provide effective therapy in a murine model of adult T-cell leukemia by a mechanism other than blockade of IL-2/IL-2R alpha interaction. Cancer Res 60:6977–6984, 2000
Zhang M, Zhang Z, Garmestani K, Goldman CK, Ravetch JV, Brechbiel MW, Carrasquillo JA, Waldmann TA: Activating Fc receptors are required for antitumor efficacy of the antibodies directed toward CD25 in a murine model of adult T-cell leukemia. Cancer Res 64:5825–5829, 2004
Tan C, Waldmann TA: Proteasome inhibitor PS-341 a potential therapeutic agent for adult T-cell leukemia. Cancer Res 62:1083–1086, 2002
Zhang M, Zhang Z, Goldman CK, Janik J, Waldmann TA: Combination therapy for adult T-cell leukemia-xenografted mice: Flavopiridol and anti-CD25 monoclonal antibody. Blood 105:1231–1236, 2005
Kreitman RJ, Wilson WH, White JD, Stetler-Stevenson M, Jaffe ES, Giardina S, Waldmann TA, Pastan I: Phase I trial of recombinant immunotoxin anti-Tac(Fv)-PE38 (LMB-2) in patients with hematologic malignancies. J Clin Oncol 18:1622–1636, 2000
Axworthy DB, Reno JM, Hylarides MD, Mallett RW, Theodore LJ, Gustavson LM, Su F, Hobson LJ, Beaumier PL, Fritzberg AR: Cure of human carcinoma xenografts by a single dose of pretargeted yttrium-90 with negligible toxicity. Proc Natl Acad Sci USA 97:1802–1807, 2000
Zhang M, Yao Z, Garmestani K, Axworthy DB, Zhang Z, Mallett RW, Theodore LJ, Goldman CK, Brechbiel MW, Carrasquillo JA, Waldmann TA: Pretargeting radioimmunotherapy of a murine model of adult T-cell leukemia with the alpha-emitting radionuclide bismuth. Blood 100:208–216, 2002
Zhang M, Zhang Z, Garmestani K, Schultz J, Axworthy DB, Goldman CK, Brechbiel MW, Carrasquillo JA, Waldmann TA: Pretarget radiotherapy with an anti-CD25 antibody-streptavidin fusion protein was effective in therapy of leukemia/lymphoma xenografts. Proc Natl Acad Sci USA 100:1891–1895, 2003
Zhang M, Yao Z, Zhang Z, Garmestani K, Talanov VS, Plascjak PS, Yu S, Kim HS, Goldman CK, Paik CH, Brechbiel MW, Carrasquillo JA, Waldmann TA: The Anti-CD25 monoclonal antibody 7G7/B6 armed with the {alpha}-emitter 211At provides effective radioimmunotherapy for a murine model of leukemia. Cancer Res 66:8227–8232, 2006
Sloand EM, Scheinberg P, Maciejewski J, Young NS: Brief communication: Successful treatment of pure red-cell aplasia with an anti-interleukin-2 receptor antibody (daclizumab). Ann Intern Med 144:181–185, 2006
Maciejewski JP, Sloand EM, Nunez O, Boss C, Young NS: Recombinant humanized anti-IL-2 receptor antibody (daclizumab) produces responses in patients with moderate aplastic anemia. Blood 102:3584–3586, 2003
Guex-Crosier Y, Raber J, Chan CC, Kriete MS, Benichou J, Pilson RS, Kerwin JA, Waldmann TA, Hakimi J, Roberge FG: Humanized antibodies against the alpha-chain of the IL-2 receptor and against the beta-chain shared by the IL-2 and IL-15 receptors in a monkey uveitis model of autoimmune diseases. J Immunol 158:452–458, 1997
Krueger JG, Walters IB, Miyazawa M, Gilleaudeau P, Hakimi J, Light S, Sherr A, Gottlieb AB: Successful in vivo blockade of CD25 (high-affinity interleukin-2 receptor) on T-cells by administration of humanized anti-Tac antibody to patients with psoriasis. J Am Acad Dermatol 43:448–458, 2000
Rose JW, Watt HE, White AT, Carlson NG: Treatment of multiple sclerosis with an anti-interleukin-2 receptor monoclonal antibody. Ann Neurol 56:864–867, 2004
Bielekova B, Howard T, Packer A, Richert N, Blevins G, O’Hayon J, Waldmann TA, McFarland HF, Martin R: Daclizumab inhibits inflammation and stabilizes disease progression in multiple sclerosis. Ann Neurol, in press
Tendler CL, Greenberg SJ, Blattner WA, Manns A, Murphy E, Fleisher T, Hanchard B, Morgan O, Burton JD, Nelson DL, Waldmann TA: Transactivation of interleukin 2 and its receptor induces immune activation in human T-cell lymphotropic virus type I-associated myelopathy: pathogenic implications and a rationale for immunotherapy. Proc Natl Acad Sci USA 87:5218–5222, 1990
Azimi N, Brown K, Bamford RN, Tagaya Y, Siebenlist U, Waldmann TA: Human T-cell lymphotropic virus type I Tax protein trans-activates interleukin 15 gene transcription through an NF-kappaB site. Proc Natl Acad Sci USA 95:2452–2457, 1998
Azimi N, Nagai M, Jacobson S, Waldmann TA: IL-15 plays a major role in the persistence of Tax-specific CD8 cells in HAM/TSP patients. Proc Natl Acad Sci USA 98:14559–14564, 2001
Tkaczuk J, Yu CL, Baksh S, Milford EL, Carpenter CB, Burakoff SJ, McKay DB: Effect of anti-IL-2Ralpha antibody on IL-2-induced Jak/STAT signaling. Am J Transplant 2:31–40, 2002
Goebel J, Stevens E, Forrest K, Roszman TL: Daclizumab (Zenapax) inhibits early interleukin-2 receptor signal transduction events. Transpl Immunol 8:153–159, 2000
Bielekova B, Catalfamo M, Reichert-Scrivner S, Packer A, Cerna M, Waldmann TA, McFarland H, Henkart PA, Martin R: Regulatory CD56(bright) natural killer cells mediate immunomodulatory effects of IL-2R alpha-targeted therapy (daclizumab) in multiple sclerosis. Proc Natl Acad Sci USA 103:5941–5946, 2006
Li Z, Lim WK, Mahesh SP, Liu B, Nussenblatt RB: Cutting edge: In vivo blockade of human IL-2 receptor induces expansion of CD56(bright) regulatory NK cells in patients with active uveitis. J Immunol 174:5187–5191, 2005
Zhang B, Yamamura T, Kondo T, Fujiwara M, Tabira T: Regulation of experimental autoimmune encephalomyelitis by natural killer (NK) cells. J Exp Med 186:1677–1687, 1997
Brok HP, Tekoppele JM, Hakimi J, Kerwin JA, Nijenhuis EM, De Groot CW, Bontrop RE, Hart BA: Prophylactic and therapeutic effects of a humanized monoclonal antibody against the IL-2 receptor (DACLIZUMAB) on collagen-induced arthritis (CIA) in rhesus monkeys. Clin Exp Immunol 124:134–141, 2001
ACKNOWLEDGMENTS
This work was supported by the Intramural Research Program of the National Cancer Institute, NIH. All animal studies were approved by the Animal Care and Use Committee of the National Cancer Institute (NCI) and all clinical investigations had prior approval of the IRB, NCI.
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Waldmann, T.A. Anti-Tac (daclizumab, Zenapax) in the Treatment of Leukemia, Autoimmune Diseases, and in the Prevention of Allograft Rejection: A 25-Year Personal Odyssey. J Clin Immunol 27, 1–18 (2007). https://doi.org/10.1007/s10875-006-9060-0
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DOI: https://doi.org/10.1007/s10875-006-9060-0