{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T19:22:44Z","timestamp":1791400964174,"version":"4.3.3"},"publisher-location":"Cham","reference-count":92,"publisher":"Springer International Publishing","isbn-type":[{"value":"9783319531557","type":"print"},{"value":"9783319531564","type":"electronic"}],"license":[{"start":{"date-parts":[[2017,1,1]],"date-time":"2017-01-01T00:00:00Z","timestamp":1483228800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2017,1,1]],"date-time":"2017-01-01T00:00:00Z","timestamp":1483228800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017]]},"DOI":"10.1007\/978-3-319-53156-4_2","type":"book-chapter","created":{"date-parts":[[2017,3,20]],"date-time":"2017-03-20T09:32:35Z","timestamp":1490002355000},"page":"33-51","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["Interleukin-2: Old and New Approaches to Enhance Immune-Therapeutic Efficacy"],"prefix":"10.1007","author":[{"given":"Pooja","family":"Dhupkar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Gordon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,3,21]]},"reference":[{"issue":"1","key":"2_CR1","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1016\/0092-8674(93)90152-G","volume":"73","author":"T Taniguchi","year":"1993","unstructured":"Taniguchi T, Minami Y. The IL-2\/IL-2 receptor system: a current overview. Cell. 1993;73(1):5\u20138.","journal-title":"Cell"},{"issue":"1","key":"2_CR2","doi-asserted-by":"crossref","first-page":"157","DOI":"10.4049\/jimmunol.134.1.157","volume":"134","author":"MT Lotze","year":"1985","unstructured":"Lotze MT, et al. In vivo administration of purified human interleukin 2. I. Half-life and immunologic effects of the Jurkat cell line-derived interleukin 2. J Immunol. 1985;134(1):157\u201366.","journal-title":"J Immunol"},{"issue":"4","key":"2_CR3","doi-asserted-by":"crossref","first-page":"2865","DOI":"10.4049\/jimmunol.135.4.2865","volume":"135","author":"MT Lotze","year":"1985","unstructured":"Lotze MT, et al. In vivo administration of purified human interleukin 2. II. Half life, immunologic effects, and expansion of peripheral lymphoid cells in vivo with recombinant IL 2. J Immunol. 1985;135(4):2865\u201375.","journal-title":"J Immunol"},{"issue":"6 Suppl 6","key":"2_CR4","first-page":"10","volume":"15","author":"DR Parkinson","year":"1988","unstructured":"Parkinson DR. Interleukin-2 in cancer therapy. Semin Oncol. 1988;15(6 Suppl 6):10\u201326.","journal-title":"Semin Oncol"},{"issue":"5","key":"2_CR5","doi-asserted-by":"publisher","first-page":"1169","DOI":"10.1084\/jem.161.5.1169","volume":"161","author":"SA Rosenberg","year":"1985","unstructured":"Rosenberg SA, et al. Regression of established pulmonary metastases and subcutaneous tumor mediated by the systemic administration of high-dose recombinant interleukin 2. J Exp Med. 1985;161(5):1169\u201388.","journal-title":"J Exp Med"},{"key":"2_CR6","first-page":"391967","volume":"2014","author":"SP D\u2019Angelo","year":"2014","unstructured":"D\u2019Angelo SP, et al. Sarcoma immunotherapy: past approaches and future directions. Sarcoma. 2014;2014:391967.","journal-title":"Sarcoma"},{"issue":"2","key":"2_CR7","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1136\/gut.28.2.113","volume":"28","author":"EA Fagan","year":"1987","unstructured":"Fagan EA, Eddleston AL. Immunotherapy for cancer: the use of lymphokine activated killer (LAK) cells. Gut. 1987;28(2):113\u20136.","journal-title":"Gut"},{"issue":"6","key":"2_CR8","doi-asserted-by":"publisher","first-page":"1823","DOI":"10.1084\/jem.155.6.1823","volume":"155","author":"EA Grimm","year":"1982","unstructured":"Grimm EA, et al. 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. 1982;155(6):1823\u201341.","journal-title":"J Exp Med"},{"issue":"14","key":"2_CR9","first-page":"3669","volume":"51","author":"SC Yang","year":"1991","unstructured":"Yang SC, et al. Clinical and immunomodulatory effects of combination immunotherapy with low-dose interleukin 2 and tumor necrosis factor alpha in patients with advanced non-small cell lung cancer: a phase I trial. Cancer Res. 1991;51(14):3669\u201376.","journal-title":"Cancer Res"},{"issue":"3","key":"2_CR10","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1007\/BF00199995","volume":"29","author":"SC Yang","year":"1989","unstructured":"Yang SC, et al. Induction of lymphokine-activated killer cytotoxicity with interleukin-2 and tumor necrosis factor-alpha against primary lung cancer targets. Cancer Immunol Immunother. 1989;29(3):193\u20138.","journal-title":"Cancer Immunol Immunother"},{"issue":"8","key":"2_CR11","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1093\/jnci\/85.8.622","volume":"85","author":"SA Rosenberg","year":"1993","unstructured":"Rosenberg SA, et al. 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 Inst. 1993;85(8):622\u201332.","journal-title":"J Natl Cancer Inst"},{"issue":"2","key":"2_CR12","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1084\/jem.159.2.495","volume":"159","author":"A Mazumder","year":"1984","unstructured":"Mazumder A, Rosenberg SA. Successful immunotherapy of natural killer-resistant established pulmonary melanoma metastases by the intravenous adoptive transfer of syngeneic lymphocytes activated in vitro by interleukin 2. J Exp Med. 1984;159(2):495\u2013507.","journal-title":"J Exp Med"},{"issue":"4669","key":"2_CR13","doi-asserted-by":"publisher","first-page":"1487","DOI":"10.1126\/science.6332379","volume":"225","author":"JJ Mule","year":"1984","unstructured":"Mule JJ, et al. Adoptive immunotherapy of established pulmonary metastases with LAK cells and recombinant interleukin-2. Science. 1984;225(4669):1487\u20139.","journal-title":"Science"},{"issue":"1","key":"2_CR14","doi-asserted-by":"crossref","first-page":"646","DOI":"10.4049\/jimmunol.135.1.646","volume":"135","author":"JJ Mule","year":"1985","unstructured":"Mule JJ, Shu S, Rosenberg SA. The anti-tumor efficacy of lymphokine-activated killer cells and recombinant interleukin 2 in vivo. J Immunol. 1985;135(1):646\u201352.","journal-title":"J Immunol"},{"issue":"8","key":"2_CR15","first-page":"3735","volume":"45","author":"R Lafreniere","year":"1985","unstructured":"Lafreniere R, Rosenberg SA. Successful immunotherapy of murine experimental hepatic metastases with lymphokine-activated killer cells and recombinant interleukin 2. Cancer Res. 1985;45(8):3735\u201341.","journal-title":"Cancer Res"},{"issue":"6","key":"2_CR16","doi-asserted-by":"crossref","first-page":"4273","DOI":"10.4049\/jimmunol.135.6.4273","volume":"135","author":"R Lafreniere","year":"1985","unstructured":"Lafreniere R, Rosenberg SA. 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 nonimmunogenic sarcomas and an adenocarcinoma. J Immunol. 1985;135(6):4273\u201380.","journal-title":"J Immunol"},{"issue":"23","key":"2_CR17","doi-asserted-by":"publisher","first-page":"1485","DOI":"10.1056\/NEJM198512053132327","volume":"313","author":"SA Rosenberg","year":"1985","unstructured":"Rosenberg SA, et al. Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2 to patients with metastatic cancer. N Engl J Med. 1985;313(23):1485\u201392.","journal-title":"N Engl J Med"},{"issue":"12","key":"2_CR18","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1001\/jama.1994.03510360033032","volume":"271","author":"SA Rosenberg","year":"1994","unstructured":"Rosenberg SA, et al. Treatment of 283 consecutive patients with metastatic melanoma or renal cell cancer using high-dose bolus interleukin 2. JAMA. 1994;271(12):907\u201313.","journal-title":"JAMA"},{"issue":"7","key":"2_CR19","doi-asserted-by":"publisher","first-page":"2105","DOI":"10.1200\/JCO.1999.17.7.2105","volume":"17","author":"MB Atkins","year":"1999","unstructured":"Atkins MB, et al. High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. J Clin Oncol. 1999;17(7):2105\u201316.","journal-title":"J Clin Oncol"},{"issue":"6","key":"2_CR20","doi-asserted-by":"publisher","first-page":"951","DOI":"10.1038\/bjc.1996.463","volume":"74","author":"WH Kruit","year":"1996","unstructured":"Kruit WH, et al. Dose efficacy study of two schedules of high-dose bolus administration of interleukin 2 and interferon alpha in metastatic melanoma. Br J Cancer. 1996;74(6):951\u20135.","journal-title":"Br J Cancer"},{"issue":"2","key":"2_CR21","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1002\/1097-0142(19930715)72:2<607::AID-CNCR2820720245>3.0.CO;2-R","volume":"72","author":"U Keilholz","year":"1993","unstructured":"Keilholz U, et al. Interferon-alpha and interleukin-2 in the treatment of metastatic melanoma. Comparison of two phase II trials. Cancer. 1993;72(2):607\u201314.","journal-title":"Cancer"},{"issue":"4","key":"2_CR22","first-page":"1267","volume":"6","author":"GC de Gast","year":"2000","unstructured":"de Gast GC, et al. Phase I trial of combined immunotherapy with subcutaneous granulocyte macrophage colony-stimulating factor, low-dose interleukin 2, and interferon alpha in progressive metastatic melanoma and renal cell carcinoma. Clin Cancer Res. 2000;6(4):1267\u201372.","journal-title":"Clin Cancer Res"},{"issue":"Suppl 1","key":"2_CR23","first-page":"S73","volume":"3","author":"JP Dutcher","year":"1997","unstructured":"Dutcher JP, et al. Interleukin-2-based therapy for metastatic renal cell cancer: the Cytokine Working Group experience, 1989-1997. Cancer J Sci Am. 1997;3(Suppl 1):S73\u20138.","journal-title":"Cancer J Sci Am"},{"key":"2_CR24","doi-asserted-by":"crossref","unstructured":"Rosenberg SA, et al. Experience with the use of high-dose interleukin-2 in the treatment of 652 cancer patients. Ann Surg. 1989; 210(4):474\u201384; discussion 484\u20135.","DOI":"10.1097\/00000658-198910000-00008"},{"issue":"7","key":"2_CR25","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.1093\/annonc\/mdi226","volume":"16","author":"W Schwinger","year":"2005","unstructured":"Schwinger W, et al. Feasibility of high-dose interleukin-2 in heavily pretreated pediatric cancer patients. Ann Oncol. 2005;16(7):1199\u2013206.","journal-title":"Ann Oncol"},{"issue":"5","key":"2_CR26","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.4049\/jimmunol.137.5.1735","volume":"137","author":"M Rosenstein","year":"1986","unstructured":"Rosenstein M, Ettinghausen SE, Rosenberg SA. Extravasation of intravascular fluid mediated by the systemic administration of recombinant interleukin-2. J Immunol. 1986;137(5):1735\u201342.","journal-title":"J Immunol"},{"issue":"1","key":"2_CR27","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1186\/1479-5876-2-17","volume":"2","author":"MC Panelli","year":"2004","unstructured":"Panelli MC, et al. Forecasting the cytokine storm following systemic interleukin (IL)-2 administration. J Transl Med. 2004;2(1):17.","journal-title":"J Transl Med"},{"issue":"12","key":"2_CR28","doi-asserted-by":"publisher","first-page":"2764","DOI":"10.1002\/1097-0142(19861215)58:12<2764::AID-CNCR2820581235>3.0.CO;2-Z","volume":"58","author":"MT Lotze","year":"1986","unstructured":"Lotze MT, et al. Clinical effects and toxicity of interleukin-2 in patients with cancer. Cancer. 1986;58(12):2764\u201372.","journal-title":"Cancer"},{"issue":"3","key":"2_CR29","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1038\/nri3156","volume":"12","author":"O Boyman","year":"2012","unstructured":"Boyman O, Sprent J. The role of interleukin-2 during homeostasis and activation of the immune system. Nat Rev Immunol. 2012;12(3):180\u201390.","journal-title":"Nat Rev Immunol"},{"issue":"12","key":"2_CR30","doi-asserted-by":"publisher","first-page":"1323","DOI":"10.1517\/14712598.6.12.1323","volume":"6","author":"O Boyman","year":"2006","unstructured":"Boyman O, Surh CD, Sprent J. Potential use of IL-2\/anti-IL-2 antibody immune complexes for the treatment of cancer and autoimmune disease. Expert Opin Biol Ther. 2006;6(12):1323\u201331.","journal-title":"Expert Opin Biol Ther"},{"issue":"4","key":"2_CR31","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1016\/0002-9343(90)90507-A","volume":"88","author":"LM Schuchter","year":"1990","unstructured":"Schuchter LM, et al. Eosinophilic myocarditis associated with high-dose interleukin-2 therapy. Am J Med. 1990;88(4):439\u201340.","journal-title":"Am J Med"},{"issue":"14","key":"2_CR32","doi-asserted-by":"publisher","first-page":"959","DOI":"10.1056\/NEJM199004053221404","volume":"322","author":"MS Klempner","year":"1990","unstructured":"Klempner MS, et al. An acquired chemotactic defect in neutrophils from patients receiving interleukin-2 immunotherapy. N Engl J Med. 1990;322(14):959\u201365.","journal-title":"N Engl J Med"},{"issue":"5","key":"2_CR33","doi-asserted-by":"crossref","first-page":"2203","DOI":"10.4049\/jimmunol.130.5.2203","volume":"130","author":"JH Donohue","year":"1983","unstructured":"Donohue JH, Rosenberg SA. The fate of interleukin-2 after in vivo administration. J Immunol. 1983;130(5):2203\u20138.","journal-title":"J Immunol"},{"issue":"7","key":"2_CR34","doi-asserted-by":"publisher","first-page":"2268","DOI":"10.1002\/jps.21596","volume":"98","author":"MA Shaker","year":"2009","unstructured":"Shaker MA, Younes HM. Interleukin-2: evaluation of routes of administration and current delivery systems in cancer therapy. J Pharm Sci. 2009;98(7):2268\u201398.","journal-title":"J Pharm Sci"},{"issue":"7","key":"2_CR35","first-page":"2009","volume":"50","author":"MW Konrad","year":"1990","unstructured":"Konrad MW, et al. Pharmacokinetics of recombinant interleukin 2 in humans. Cancer Res. 1990;50(7):2009\u201317.","journal-title":"Cancer Res"},{"issue":"1","key":"2_CR36","doi-asserted-by":"publisher","first-page":"19","DOI":"10.2165\/00003088-199427010-00003","volume":"27","author":"PM Anderson","year":"1994","unstructured":"Anderson PM, Sorenson MA. Effects of route and formulation on clinical pharmacokinetics of interleukin-2. Clin Pharmacokinet. 1994;27(1):19\u201331.","journal-title":"Clin Pharmacokinet"},{"issue":"4","key":"2_CR37","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1002\/(SICI)1097-0142(19980815)83:4<797::AID-CNCR25>3.0.CO;2-M","volume":"83","author":"US Kammula","year":"1998","unstructured":"Kammula US, White DE, Rosenberg SA. Trends in the safety of high dose bolus interleukin-2 administration in patients with metastatic cancer. Cancer. 1998;83(4):797\u2013805.","journal-title":"Cancer"},{"issue":"7","key":"2_CR38","doi-asserted-by":"publisher","first-page":"1409","DOI":"10.1002\/(SICI)1097-0142(19970401)79:7<1409::AID-CNCR19>3.0.CO;2-3","volume":"79","author":"C Khanna","year":"1997","unstructured":"Khanna C, et al. Interleukin-2 liposome inhalation therapy is safe and effective for dogs with spontaneous pulmonary metastases. Cancer. 1997;79(7):1409\u201321.","journal-title":"Cancer"},{"issue":"10","key":"2_CR39","doi-asserted-by":"publisher","first-page":"960","DOI":"10.1111\/j.2042-7158.1997.tb06024.x","volume":"49","author":"C Khanna","year":"1997","unstructured":"Khanna C, et al. Nebulized interleukin 2 liposomes: aerosol characteristics and biodistribution. J Pharm Pharmacol. 1997;49(10):960\u201371.","journal-title":"J Pharm Pharmacol"},{"issue":"8","key":"2_CR40","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1089\/hum.2005.16.937","volume":"16","author":"S Dow","year":"2005","unstructured":"Dow S, et al. Phase I study of liposome-DNA complexes encoding the interleukin-2 gene in dogs with osteosarcoma lung metastases. Hum Gene Ther. 2005;16(8):937\u201346.","journal-title":"Hum Gene Ther"},{"issue":"3","key":"2_CR41","doi-asserted-by":"publisher","first-page":"638","DOI":"10.2337\/diabetes.51.3.638","volume":"51","author":"A Rabinovitch","year":"2002","unstructured":"Rabinovitch A, et al. Combination therapy with sirolimus and interleukin-2 prevents spontaneous and recurrent autoimmune diabetes in NOD mice. Diabetes. 2002;51(3):638\u201345.","journal-title":"Diabetes"},{"key":"2_CR42","doi-asserted-by":"crossref","unstructured":"Shin JI, Park SJ, Kim JH. A possible role of leptin-associated increase in soluble interleukin-2 receptor diminishing a clinical response to infliximab in rheumatoid arthritis: comment on the article by Klaasen et al. Arthritis Rheum. 2011;63(9):2833\u20134; author reply 2834.","DOI":"10.1002\/art.30462"},{"issue":"8","key":"2_CR43","doi-asserted-by":"publisher","first-page":"4904","DOI":"10.4049\/jimmunol.0900284","volume":"183","author":"J Tomala","year":"2009","unstructured":"Tomala J, et al. In vivo expansion of activated naive CD8+ T cells and NK cells driven by complexes of IL-2 and anti-IL-2 monoclonal antibody as novel approach of cancer immunotherapy. J Immunol. 2009;183(8):4904\u201312.","journal-title":"J Immunol"},{"issue":"1\u20132","key":"2_CR44","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.imlet.2014.01.017","volume":"159","author":"P Votavova","year":"2014","unstructured":"Votavova P, Tomala J, Kovar M. Increasing the biological activity of IL-2 and IL-15 through complexing with anti-IL-2 mAbs and IL-15Ralpha-Fc chimera. Immunol Lett. 2014;159(1\u20132):1\u201310.","journal-title":"Immunol Lett"},{"issue":"26","key":"2_CR45","doi-asserted-by":"publisher","first-page":"11906","DOI":"10.1073\/pnas.1002569107","volume":"107","author":"C Krieg","year":"2010","unstructured":"Krieg C, et al. Improved IL-2 immunotherapy by selective stimulation of IL-2 receptors on lymphocytes and endothelial cells. Proc Natl Acad Sci U S A. 2010;107(26):11906\u201311.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"5","key":"2_CR46","doi-asserted-by":"publisher","first-page":"2171","DOI":"10.1073\/pnas.0909384107","volume":"107","author":"S Letourneau","year":"2010","unstructured":"Letourneau S, et al. IL-2\/anti-IL-2 antibody complexes show strong biological activity by avoiding interaction with IL-2 receptor alpha subunit CD25. Proc Natl Acad Sci U S A. 2010;107(5):2171\u20136.","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"7395","key":"2_CR47","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1038\/nature10975","volume":"484","author":"AM Levin","year":"2012","unstructured":"Levin AM, et al. Exploiting a natural conformational switch to engineer an interleukin-2 \u2018superkine\u2019. Nature. 2012;484(7395):529\u201333.","journal-title":"Nature"},{"issue":"1","key":"2_CR48","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.imbio.2012.02.009","volume":"218","author":"G Rojas","year":"2013","unstructured":"Rojas G, et al. Deciphering the molecular bases of the biological effects of antibodies against interleukin-2: a versatile platform for fine epitope mapping. Immunobiology. 2013;218(1):105\u201313.","journal-title":"Immunobiology"},{"issue":"1","key":"2_CR49","doi-asserted-by":"publisher","first-page":"273","DOI":"10.4161\/mabs.27224","volume":"6","author":"G Rojas","year":"2014","unstructured":"Rojas G, et al. Fine epitope specificity of antibodies against interleukin-2 explains their paradoxical immunomodulatory effects. MAbs. 2014;6(1):273\u201385.","journal-title":"MAbs"},{"issue":"12","key":"2_CR50","doi-asserted-by":"publisher","first-page":"6230","DOI":"10.4049\/jimmunol.1201895","volume":"190","author":"T Carmenate","year":"2013","unstructured":"Carmenate T, et al. Human IL-2 mutein with higher antitumor efficacy than wild type IL-2. J Immunol. 2013;190(12):6230\u20138.","journal-title":"J Immunol"},{"issue":"1","key":"2_CR51","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1007\/s10555-014-9542-0","volume":"34","author":"A Rotte","year":"2015","unstructured":"Rotte A, et al. Immunotherapy of melanoma: present options and future promises. Cancer Metastasis Rev. 2015;34(1):115\u201328.","journal-title":"Cancer Metastasis Rev"},{"issue":"11","key":"2_CR52","doi-asserted-by":"publisher","first-page":"3673","DOI":"10.1158\/1078-0432.CCR-10-2921","volume":"17","author":"SD Gillies","year":"2011","unstructured":"Gillies SD, et al. A low-toxicity IL-2-based immunocytokine retains antitumor activity despite its high degree of IL-2 receptor selectivity. Clin Cancer Res. 2011;17(11):3673\u201385.","journal-title":"Clin Cancer Res"},{"issue":"12","key":"2_CR53","doi-asserted-by":"publisher","first-page":"1789","DOI":"10.1007\/s00262-011-1072-9","volume":"60","author":"JA Gubbels","year":"2011","unstructured":"Gubbels JA, et al. Ab-IL2 fusion proteins mediate NK cell immune synapse formation by polarizing CD25 to the target cell-effector cell interface. Cancer Immunol Immunother. 2011;60(12):1789\u2013800.","journal-title":"Cancer Immunol Immunother"},{"issue":"1","key":"2_CR54","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.ejca.2012.07.015","volume":"49","author":"S Gillessen","year":"2013","unstructured":"Gillessen S, et al. A phase I dose-escalation study of the immunocytokine EMD 521873 (Selectikine) in patients with advanced solid tumours. Eur J Cancer. 2013;49(1):35\u201344.","journal-title":"Eur J Cancer"},{"issue":"Suppl 2","key":"2_CR55","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1186\/2051-1426-2-S2-I8","volume":"2","author":"C Klein","year":"2014","unstructured":"Klein C. Novel CEA-targeted IL-2 variant immunocytokine for immunotherapy of cancer. J ImmunoTherapy Cancer. 2014;2(Suppl 2):18.","journal-title":"J ImmunoTherapy Cancer"},{"issue":"18","key":"2_CR56","doi-asserted-by":"publisher","first-page":"5923","DOI":"10.1158\/1078-0432.CCR-08-2963","volume":"15","author":"JA Hank","year":"2009","unstructured":"Hank JA, et al. Immunogenicity of the hu14.18-IL2 immunocytokine molecule in adults with melanoma and children with neuroblastoma. Clin Cancer Res. 2009;15(18):5923\u201330.","journal-title":"Clin Cancer Res"},{"issue":"33","key":"2_CR57","doi-asserted-by":"publisher","first-page":"4969","DOI":"10.1200\/JCO.2009.27.8861","volume":"28","author":"S Shusterman","year":"2010","unstructured":"Shusterman S, et al. Antitumor activity of hu14.18-IL2 in patients with relapsed\/refractory neuroblastoma: a Children\u2019s Oncology Group (COG) phase II study. J Clin Oncol. 2010;28(33):4969\u201375.","journal-title":"J Clin Oncol"},{"issue":"6","key":"2_CR58","doi-asserted-by":"publisher","first-page":"1839","DOI":"10.1200\/JCO.2001.19.6.1839","volume":"19","author":"S Sharma","year":"2001","unstructured":"Sharma S, et al. Development of inhalational agents for oncologic use. J Clin Oncol. 2001;19(6):1839\u201347.","journal-title":"J Clin Oncol"},{"issue":"8","key":"2_CR59","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1038\/nrc1893","volume":"6","author":"AI Minchinton","year":"2006","unstructured":"Minchinton AI, Tannock IF. Drug penetration in solid tumours. Nat Rev Cancer. 2006;6(8):583\u201392.","journal-title":"Nat Rev Cancer"},{"issue":"1","key":"2_CR60","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1089\/jamp.2007.0656","volume":"21","author":"F Gagnadoux","year":"2008","unstructured":"Gagnadoux F, et al. Aerosolized chemotherapy. J Aerosol Med Pulm Drug Deliv. 2008;21(1):61\u201370.","journal-title":"J Aerosol Med Pulm Drug Deliv"},{"issue":"4","key":"2_CR61","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1093\/annonc\/mdh137","volume":"15","author":"O Merimsky","year":"2004","unstructured":"Merimsky O, et al. Targeting pulmonary metastases of renal cell carcinoma by inhalation of interleukin-2. Ann Oncol. 2004;15(4):610\u20132.","journal-title":"Ann Oncol"},{"issue":"7","key":"2_CR62","first-page":"1115","volume":"2","author":"J Lorenz","year":"1996","unstructured":"Lorenz J, et al. Phase I trial of inhaled natural interleukin 2 for treatment of pulmonary malignancy: toxicity, pharmacokinetics, and biological effects. Clin Cancer Res. 1996;2(7):1115\u201322.","journal-title":"Clin Cancer Res"},{"issue":"8","key":"2_CR63","doi-asserted-by":"publisher","first-page":"1362","DOI":"10.1002\/pbc.25019","volume":"61","author":"SR Guma","year":"2014","unstructured":"Guma SR, et al. Aerosol interleukin-2 induces natural killer cell proliferation in the lung and combination therapy improves the survival of mice with osteosarcoma lung metastasis. Pediatr Blood Cancer. 2014;61(8):1362\u20138.","journal-title":"Pediatr Blood Cancer"},{"issue":"4","key":"2_CR64","doi-asserted-by":"publisher","first-page":"618","DOI":"10.1002\/pbc.24801","volume":"61","author":"SR Guma","year":"2014","unstructured":"Guma SR, et al. Natural killer cell therapy and aerosol interleukin-2 for the treatment of osteosarcoma lung metastasis. Pediatr Blood Cancer. 2014;61(4):618\u201326.","journal-title":"Pediatr Blood Cancer"},{"issue":"1","key":"2_CR65","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1158\/0008-5472.CAN-11-2778","volume":"72","author":"GX Huang","year":"2012","unstructured":"Huang GX, et al. Genetically modified T cells targeting interleukin-11 receptor alpha-chain kill human osteosarcoma cells and induce the regression of established osteosarcoma lung metastases. Cancer Res. 2012;72(1):271\u201381.","journal-title":"Cancer Res"},{"issue":"4","key":"2_CR66","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1200\/JCO.1993.11.4.661","volume":"11","author":"MB Atkins","year":"1993","unstructured":"Atkins MB, et al. Randomized phase II trial of high-dose interleukin-2 either alone or in combination with interferon alfa-2b in advanced renal cell carcinoma. J Clin Oncol. 1993;11(4):661\u201370.","journal-title":"J Clin Oncol"},{"issue":"10","key":"2_CR67","doi-asserted-by":"publisher","first-page":"1969","DOI":"10.1200\/JCO.1993.11.10.1969","volume":"11","author":"JA Sparano","year":"1993","unstructured":"Sparano JA, et al. Randomized phase III trial of treatment with high-dose interleukin-2 either alone or in combination with interferon alfa-2a in patients with advanced melanoma. J Clin Oncol. 1993;11(10):1969\u201377.","journal-title":"J Clin Oncol"},{"issue":"9","key":"2_CR68","doi-asserted-by":"publisher","first-page":"2921","DOI":"10.1200\/JCO.1998.16.9.2921","volume":"16","author":"U Keilholz","year":"1998","unstructured":"Keilholz U, et al. Results of interleukin-2-based treatment in advanced melanoma: a case record-based analysis of 631 patients. J Clin Oncol. 1998;16(9):2921\u20139.","journal-title":"J Clin Oncol"},{"issue":"4","key":"2_CR69","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1054\/bjoc.1999.0997","volume":"82","author":"CM van Herpen","year":"2000","unstructured":"van Herpen CM, et al. Immunochemotherapy with interleukin-2, interferon-alpha and 5-fluorouracil for progressive metastatic renal cell carcinoma: a multicenter phase II study. Dutch Immunotherapy Working Party. Br J Cancer. 2000;82(4):772\u20136.","journal-title":"Br J Cancer"},{"issue":"7","key":"2_CR70","doi-asserted-by":"publisher","first-page":"1632","DOI":"10.1002\/cncr.23791","volume":"113","author":"AA Tarhini","year":"2008","unstructured":"Tarhini AA, et al. A phase 2 trial of sequential temozolomide chemotherapy followed by high-dose interleukin 2 immunotherapy for metastatic melanoma. Cancer. 2008;113(7):1632\u201340.","journal-title":"Cancer"},{"issue":"4","key":"2_CR71","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1586\/14737140.7.4.433","volume":"7","author":"RL Panares","year":"2007","unstructured":"Panares RL, Garcia AA. Bevacizumab in the management of solid tumors. Expert Rev Anticancer Ther. 2007;7(4):433\u201345.","journal-title":"Expert Rev Anticancer Ther"},{"issue":"3","key":"2_CR72","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.1084\/jem.179.3.1005","volume":"179","author":"AB Bakker","year":"1994","unstructured":"Bakker AB, et al. Melanocyte lineage-specific antigen gp100 is recognized by melanoma-derived tumor-infiltrating lymphocytes. J Exp Med. 1994;179(3):1005\u20139.","journal-title":"J Exp Med"},{"issue":"17","key":"2_CR73","doi-asserted-by":"publisher","first-page":"5610","DOI":"10.1158\/1078-0432.CCR-08-0116","volume":"14","author":"FO Smith","year":"2008","unstructured":"Smith FO, et al. Treatment of metastatic melanoma using interleukin-2 alone or in conjunction with vaccines. Clin Cancer Res. 2008;14(17):5610\u20138.","journal-title":"Clin Cancer Res"},{"key":"2_CR74","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/1479-5876-7-2","volume":"7","author":"HL Kaufman","year":"2009","unstructured":"Kaufman HL, et al. Phase II trial of Modified Vaccinia Ankara (MVA) virus expressing 5T4 and high dose interleukin-2 (IL-2) in patients with metastatic renal cell carcinoma. J Transl Med. 2009;7:2.","journal-title":"J Transl Med"},{"issue":"5","key":"2_CR75","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1097\/CMR.0b013e32834640c0","volume":"21","author":"MS Block","year":"2011","unstructured":"Block MS, et al. Pilot study of granulocyte-macrophage colony-stimulating factor and interleukin-2 as immune adjuvants for a melanoma peptide vaccine. Melanoma Res. 2011;21(5):438\u201345.","journal-title":"Melanoma Res"},{"issue":"32","key":"2_CR76","doi-asserted-by":"publisher","first-page":"5233","DOI":"10.1200\/JCO.2008.16.5449","volume":"26","author":"ME Dudley","year":"2008","unstructured":"Dudley ME, et al. Adoptive cell therapy for patients with metastatic melanoma: evaluation of intensive myeloablative chemoradiation preparative regimens. J Clin Oncol. 2008;26(32):5233\u20139.","journal-title":"J Clin Oncol"},{"issue":"5594","key":"2_CR77","doi-asserted-by":"publisher","first-page":"850","DOI":"10.1126\/science.1076514","volume":"298","author":"ME Dudley","year":"2002","unstructured":"Dudley ME, et al. Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science. 2002;298(5594):850\u20134.","journal-title":"Science"},{"issue":"4","key":"2_CR78","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1038\/nri3191","volume":"12","author":"NP Restifo","year":"2012","unstructured":"Restifo NP, Dudley ME, Rosenberg SA. Adoptive immunotherapy for cancer: harnessing the T cell response. Nat Rev Immunol. 2012;12(4):269\u201381.","journal-title":"Nat Rev Immunol"},{"issue":"24","key":"2_CR79","doi-asserted-by":"publisher","first-page":"6758","DOI":"10.1158\/1078-0432.CCR-12-1177","volume":"18","author":"LG Radvanyi","year":"2012","unstructured":"Radvanyi LG, et al. Specific lymphocyte subsets predict response to adoptive cell therapy using expanded autologous tumor-infiltrating lymphocytes in metastatic melanoma patients. Clin Cancer Res. 2012;18(24):6758\u201370.","journal-title":"Clin Cancer Res"},{"issue":"4","key":"2_CR80","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1097\/CJI.0b013e31819c8bda","volume":"32","author":"MJ Besser","year":"2009","unstructured":"Besser MJ, et al. Minimally cultured or selected autologous tumor-infiltrating lymphocytes after a lympho-depleting chemotherapy regimen in metastatic melanoma patients. J Immunother. 2009;32(4):415\u201323.","journal-title":"J Immunother"},{"issue":"9","key":"2_CR81","doi-asserted-by":"publisher","first-page":"2646","DOI":"10.1158\/1078-0432.CCR-10-0041","volume":"16","author":"MJ Besser","year":"2010","unstructured":"Besser MJ, et al. Clinical responses in a phase II study using adoptive transfer of short-term cultured tumor infiltration lymphocytes in metastatic melanoma patients. Clin Cancer Res. 2010;16(9):2646\u201355.","journal-title":"Clin Cancer Res"},{"key":"2_CR82","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1186\/1479-5876-10-169","volume":"10","author":"E Ellebaek","year":"2012","unstructured":"Ellebaek E, et al. Adoptive cell therapy with autologous tumor infiltrating lymphocytes and low-dose interleukin-2 in metastatic melanoma patients. J Transl Med. 2012;10:169.","journal-title":"J Transl Med"},{"issue":"1","key":"2_CR83","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1158\/0008-5472.CAN-11-2778","volume":"72","author":"G Huang","year":"2012","unstructured":"Huang G, et al. Genetically modified T cells targeting interleukin-11 receptor alpha-chain kill human osteosarcoma cells and induce the regression of established osteosarcoma lung metastases. Cancer Res. 2012;72(1):271\u201381.","journal-title":"Cancer Res"},{"issue":"9","key":"2_CR84","doi-asserted-by":"publisher","first-page":"1348","DOI":"10.3324\/haematol.2011.056747","volume":"97","author":"TK Garg","year":"2012","unstructured":"Garg TK, et al. Highly activated and expanded natural killer cells for multiple myeloma immunotherapy. Haematologica. 2012;97(9):1348\u201356.","journal-title":"Haematologica"},{"issue":"9","key":"2_CR85","doi-asserted-by":"publisher","first-page":"4010","DOI":"10.1158\/0008-5472.CAN-08-3712","volume":"69","author":"H Fujisaki","year":"2009","unstructured":"Fujisaki H, et al. Expansion of highly cytotoxic human natural killer cells for cancer cell therapy. Cancer Res. 2009;69(9):4010\u20137.","journal-title":"Cancer Res"},{"issue":"1","key":"2_CR86","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0030264","volume":"7","author":"CJ Denman","year":"2012","unstructured":"Denman CJ, et al. Membrane-bound IL-21 promotes sustained ex vivo proliferation of human natural killer cells. PLoS One. 2012;7(1):e30264.","journal-title":"PLoS One"},{"issue":"11","key":"2_CR87","doi-asserted-by":"publisher","first-page":"3699","DOI":"10.1158\/1078-0432.CCR-03-0683","volume":"10","author":"SW Krause","year":"2004","unstructured":"Krause SW, et al. Treatment of colon and lung cancer patients with ex vivo heat shock protein 70-peptide-activated, autologous natural killer cells: a clinical phase i trial. Clin Cancer Res. 2004;10(11):3699\u2013707.","journal-title":"Clin Cancer Res"},{"issue":"19","key":"2_CR88","doi-asserted-by":"publisher","first-page":"6287","DOI":"10.1158\/1078-0432.CCR-11-1347","volume":"17","author":"MR Parkhurst","year":"2011","unstructured":"Parkhurst MR, et al. Adoptive transfer of autologous natural killer cells leads to high levels of circulating natural killer cells but does not mediate tumor regression. Clin Cancer Res. 2011;17(19):6287\u201397.","journal-title":"Clin Cancer Res"},{"issue":"5562","key":"2_CR89","doi-asserted-by":"publisher","first-page":"2097","DOI":"10.1126\/science.1068440","volume":"295","author":"L Ruggeri","year":"2002","unstructured":"Ruggeri L, et al. Effectiveness of donor natural killer cell alloreactivity in mismatched hematopoietic transplants. Science. 2002;295(5562):2097\u2013100.","journal-title":"Science"},{"issue":"8","key":"2_CR90","doi-asserted-by":"publisher","first-page":"3051","DOI":"10.1182\/blood-2004-07-2974","volume":"105","author":"JS Miller","year":"2005","unstructured":"Miller JS, et al. Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer. Blood. 2005;105(8):3051\u20137.","journal-title":"Blood"},{"issue":"12","key":"2_CR91","doi-asserted-by":"publisher","first-page":"3273","DOI":"10.1182\/blood-2011-01-329508","volume":"118","author":"A Curti","year":"2011","unstructured":"Curti A, et al. Successful transfer of alloreactive haploidentical KIR ligand-mismatched natural killer cells after infusion in elderly high risk acute myeloid leukemia patients. Blood. 2011;118(12):3273\u20139.","journal-title":"Blood"},{"issue":"12","key":"2_CR92","doi-asserted-by":"publisher","first-page":"1781","DOI":"10.1007\/s00262-010-0904-3","volume":"59","author":"EG Iliopoulou","year":"2010","unstructured":"Iliopoulou EG, et al. A phase I trial of adoptive transfer of allogeneic natural killer cells in patients with advanced non-small cell lung cancer. Cancer Immunol Immunother. 2010;59(12):1781\u20139.","journal-title":"Cancer Immunol Immunother"}],"container-title":["Advances in Experimental Medicine and Biology","Immunotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/978-3-319-53156-4_2","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,25]],"date-time":"2024-01-25T10:10:00Z","timestamp":1706177400000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/978-3-319-53156-4_2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017]]},"ISBN":["9783319531557","9783319531564"],"references-count":92,"URL":"https:\/\/doi.org\/10.1007\/978-3-319-53156-4_2","relation":{},"ISSN":["0065-2598","2214-8019"],"issn-type":[{"value":"0065-2598","type":"print"},{"value":"2214-8019","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017]]},"assertion":[{"value":"21 March 2017","order":1,"name":"first_online","label":"First Online","group":{"name":"ChapterHistory","label":"Chapter History"}}]}}